CN1933827A - Use of methylene amide derivatives in cardiovascular disorders - Google Patents
Use of methylene amide derivatives in cardiovascular disorders Download PDFInfo
- Publication number
- CN1933827A CN1933827A CNA2005800087220A CN200580008722A CN1933827A CN 1933827 A CN1933827 A CN 1933827A CN A2005800087220 A CNA2005800087220 A CN A2005800087220A CN 200580008722 A CN200580008722 A CN 200580008722A CN 1933827 A CN1933827 A CN 1933827A
- Authority
- CN
- China
- Prior art keywords
- amino
- benzyl
- oxo
- acetic acid
- carbonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- WDWDWGRYHDPSDS-UHFFFAOYSA-N methanimine Chemical class N=C WDWDWGRYHDPSDS-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 208000024172 Cardiovascular disease Diseases 0.000 title claims abstract description 15
- 206010019280 Heart failures Diseases 0.000 claims abstract description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 675
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 670
- -1 hexyloxy phenyl Chemical group 0.000 claims description 512
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 338
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims description 316
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 155
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 147
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 144
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 90
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 70
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical class OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 68
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 42
- 150000001875 compounds Chemical class 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 229940073608 benzyl chloride Drugs 0.000 claims description 28
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 27
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 26
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 19
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- 239000011630 iodine Substances 0.000 claims description 18
- 125000001544 thienyl group Chemical group 0.000 claims description 16
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 15
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 14
- 125000006189 4-phenyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 230000008753 endothelial function Effects 0.000 claims description 14
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 12
- 239000005711 Benzoic acid Substances 0.000 claims description 11
- 235000010233 benzoic acid Nutrition 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 10
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 6
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 239000004593 Epoxy Substances 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- VIWJRYWUCVSZRN-UHFFFAOYSA-N 2-[(4-dodecoxynaphthalen-1-yl)methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C12=CC=CC=C2C(OCCCCCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CC1=CC=C(C(F)(F)F)C=C1 VIWJRYWUCVSZRN-UHFFFAOYSA-N 0.000 claims description 4
- YTEKIWCHDJVHMJ-UHFFFAOYSA-N 2-[(4-dodecylphenyl)methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C1=CC(CCCCCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CC1=CC=C(C(F)(F)F)C=C1 YTEKIWCHDJVHMJ-UHFFFAOYSA-N 0.000 claims description 4
- CBKVGUUFNMOQCO-UHFFFAOYSA-N 2-[2-(3-chlorophenyl)ethyl-[[4-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=CC(CN(CCC=3C=C(Cl)C=CC=3)C(=O)C(O)=O)=CC=2)=N1 CBKVGUUFNMOQCO-UHFFFAOYSA-N 0.000 claims description 4
- OWORKUNNEDPQHS-UHFFFAOYSA-N 2-[4-(trifluoromethyl)-n-[[4-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]anilino]acetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=CC(CN(CC(O)=O)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 OWORKUNNEDPQHS-UHFFFAOYSA-N 0.000 claims description 4
- REZHHDFNFZTMSK-UHFFFAOYSA-N 2-[[4-(trifluoromethyl)phenyl]methyl-[[3-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]acetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=C(CN(CC(O)=O)CC=3C=CC(=CC=3)C(F)(F)F)C=CC=2)=N1 REZHHDFNFZTMSK-UHFFFAOYSA-N 0.000 claims description 4
- NLSLBAYTEZTFDU-UHFFFAOYSA-N 2-[[4-(trifluoromethyl)phenyl]methyl-[[4-(5-undecyl-1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]acetic acid Chemical compound O1C(CCCCCCCCCCC)=NC(C=2C=CC(CN(CC(O)=O)CC=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 NLSLBAYTEZTFDU-UHFFFAOYSA-N 0.000 claims description 4
- ZHUMWUSIWQXTSQ-UHFFFAOYSA-N 2-oxo-2-[[4-(trifluoromethyl)phenyl]methyl-[[4-(3-undecyl-1,2,4-oxadiazol-5-yl)naphthalen-1-yl]methyl]amino]acetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C3=CC=CC=C3C(CN(CC=3C=CC(=CC=3)C(F)(F)F)C(=O)C(O)=O)=CC=2)=N1 ZHUMWUSIWQXTSQ-UHFFFAOYSA-N 0.000 claims description 4
- GLJMZTUTZOFEDJ-UHFFFAOYSA-N 2-oxo-2-[[4-(trifluoromethyl)phenyl]methyl-[[4-[2-(3-undecyl-1,2,4-oxadiazol-5-yl)ethyl]phenyl]methyl]amino]acetic acid Chemical compound CCCCCCCCCCCC1=NOC(CCC=2C=CC(CN(CC=3C=CC(=CC=3)C(F)(F)F)C(=O)C(O)=O)=CC=2)=N1 GLJMZTUTZOFEDJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 4
- 125000005024 alkenyl aryl group Chemical group 0.000 claims description 4
- 125000005217 alkenylheteroaryl group Chemical group 0.000 claims description 4
- 125000005025 alkynylaryl group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 4
- 241001597008 Nomeidae Species 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000006732 (C1-C15) alkyl group Chemical group 0.000 claims description 2
- VNZIIKLOIXQSDE-UHFFFAOYSA-N 2-[(1-tridecanoylpiperidin-4-yl)methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]acetic acid Chemical compound C1CN(C(=O)CCCCCCCCCCCC)CCC1CN(CC(O)=O)CC1=CC=C(C(F)(F)F)C=C1 VNZIIKLOIXQSDE-UHFFFAOYSA-N 0.000 claims description 2
- OPROHMRMQPERQH-UHFFFAOYSA-N 2-[(2-methoxyphenyl)methyl-[[3-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=C(CN(CC=3C(=CC=CC=3)OC)C(=O)C(O)=O)C=CC=2)=N1 OPROHMRMQPERQH-UHFFFAOYSA-N 0.000 claims description 2
- IIRDWUFDUKIAQO-UHFFFAOYSA-N 2-[(4-dodecoxynaphthalen-1-yl)methyl-[2-(2-fluorophenyl)ethyl]amino]-2-oxoacetic acid Chemical compound C12=CC=CC=C2C(OCCCCCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CCC1=CC=CC=C1F IIRDWUFDUKIAQO-UHFFFAOYSA-N 0.000 claims description 2
- IXSJKAJINKFVDU-UHFFFAOYSA-N 2-[(4-dodecoxynaphthalen-1-yl)methyl-[[2-(trifluoromethyl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C12=CC=CC=C2C(OCCCCCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CC1=CC=CC=C1C(F)(F)F IXSJKAJINKFVDU-UHFFFAOYSA-N 0.000 claims description 2
- IJOGKIFRKSWELU-UHFFFAOYSA-N 2-[(4-octoxyphenyl)methyl-[[2-(trifluoromethyl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C1=CC(OCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CC1=CC=CC=C1C(F)(F)F IJOGKIFRKSWELU-UHFFFAOYSA-N 0.000 claims description 2
- PJYWPFIWBMEOOK-UHFFFAOYSA-N 2-[(4-octoxyphenyl)methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C1=CC(OCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CC1=CC=C(C(F)(F)F)C=C1 PJYWPFIWBMEOOK-UHFFFAOYSA-N 0.000 claims description 2
- XZTAFXGSZGNIIU-UHFFFAOYSA-N 2-[1-benzothiophen-3-ylmethyl-[[3-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=C(CN(CC=3C4=CC=CC=C4SC=3)C(=O)C(O)=O)C=CC=2)=N1 XZTAFXGSZGNIIU-UHFFFAOYSA-N 0.000 claims description 2
- QYJQCOUVVPJSOC-UHFFFAOYSA-N 2-[1-benzothiophen-3-ylmethyl-[[4-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=CC(CN(CC=3C4=CC=CC=C4SC=3)C(=O)C(O)=O)=CC=2)=N1 QYJQCOUVVPJSOC-UHFFFAOYSA-N 0.000 claims description 2
- KXEXRDJCQVNXQT-UHFFFAOYSA-N 2-[2-(2-fluorophenyl)ethyl-[(4-octoxyphenyl)methyl]amino]-2-oxoacetic acid Chemical compound C1=CC(OCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CCC1=CC=CC=C1F KXEXRDJCQVNXQT-UHFFFAOYSA-N 0.000 claims description 2
- WNJOFKAAEKGDKD-UHFFFAOYSA-N 2-[2-(2-fluorophenyl)ethyl-[[3-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=C(CN(CCC=3C(=CC=CC=3)F)C(=O)C(O)=O)C=CC=2)=N1 WNJOFKAAEKGDKD-UHFFFAOYSA-N 0.000 claims description 2
- HJTHSPVKNUHHET-UHFFFAOYSA-N 2-[2-(2-fluorophenyl)ethyl-[[4-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=CC(CN(CCC=3C(=CC=CC=3)F)C(=O)C(O)=O)=CC=2)=N1 HJTHSPVKNUHHET-UHFFFAOYSA-N 0.000 claims description 2
- JIRKXLPXAVEKSG-UHFFFAOYSA-N 2-[[2-(trifluoromethyl)phenyl]methyl-[[4-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]acetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=CC(CN(CC(O)=O)CC=3C(=CC=CC=3)C(F)(F)F)=CC=2)=N1 JIRKXLPXAVEKSG-UHFFFAOYSA-N 0.000 claims description 2
- BWMBCMGKMDVNBU-UHFFFAOYSA-N 2-[[2-bromo-4-[2-(4-phenoxyphenyl)ethylcarbamoyl]phenyl]methyl-[(4-phenoxyphenyl)methyl]amino]-2-oxoacetic acid Chemical compound C=1C=C(C(=O)NCCC=2C=CC(OC=3C=CC=CC=3)=CC=2)C=C(Br)C=1CN(C(=O)C(=O)O)CC(C=C1)=CC=C1OC1=CC=CC=C1 BWMBCMGKMDVNBU-UHFFFAOYSA-N 0.000 claims description 2
- HEELHYUFKYLHTO-UHFFFAOYSA-N 2-[[3-(trifluoromethyl)phenyl]methyl-[[3-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]acetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=C(CN(CC(O)=O)CC=3C=C(C=CC=3)C(F)(F)F)C=CC=2)=N1 HEELHYUFKYLHTO-UHFFFAOYSA-N 0.000 claims description 2
- HFNKADFETLPTHF-UHFFFAOYSA-N 2-[[3-(trifluoromethyl)phenyl]methyl-[[4-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]acetic acid Chemical compound CCCCCCCCCCCC1=NOC(=N1)C1=CC=C(CN(CC(O)=O)CC2=CC(=CC=C2)C(F)(F)F)C=C1 HFNKADFETLPTHF-UHFFFAOYSA-N 0.000 claims description 2
- QHOLALODSGEVIM-UHFFFAOYSA-N 2-[[4-(11-hydroxyundecyl)phenyl]methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C1=CC(CCCCCCCCCCCO)=CC=C1CN(C(=O)C(O)=O)CC1=CC=C(C(F)(F)F)C=C1 QHOLALODSGEVIM-UHFFFAOYSA-N 0.000 claims description 2
- FNZIUVPXRUYCLE-UHFFFAOYSA-N 2-[[4-(dodecylcarbamoyl)phenyl]methyl-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]amino]-2-oxoacetic acid Chemical compound C1=CC(C(=O)NCCCCCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)C1CCN(C(=O)OC(C)(C)C)CC1 FNZIUVPXRUYCLE-UHFFFAOYSA-N 0.000 claims description 2
- XPJQUZXIXADECC-UHFFFAOYSA-N 2-[[4-(tridecanoylamino)phenyl]methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]acetic acid Chemical compound C1=CC(NC(=O)CCCCCCCCCCCC)=CC=C1CN(CC(O)=O)CC1=CC=C(C(F)(F)F)C=C1 XPJQUZXIXADECC-UHFFFAOYSA-N 0.000 claims description 2
- LWCBKDOSZHYODK-UHFFFAOYSA-N 2-[[4-(trifluoromethyl)phenyl]methyl-[[4-(3-undecyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]amino]acetic acid Chemical compound CCCCCCCCCCCC1=NOC(C=2C=CC(CN(CC(O)=O)CC=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 LWCBKDOSZHYODK-UHFFFAOYSA-N 0.000 claims description 2
- NHLMJKBBFKZGMH-UHFFFAOYSA-N 2-[[4-[(2-butyl-1-benzofuran-3-yl)methylcarbamoyl]phenyl]methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound CCCCC=1OC2=CC=CC=C2C=1CNC(=O)C(C=C1)=CC=C1CN(C(=O)C(O)=O)CC1=CC=C(C(F)(F)F)C=C1 NHLMJKBBFKZGMH-UHFFFAOYSA-N 0.000 claims description 2
- QWOVDAMKKHZSLJ-UHFFFAOYSA-N 2-[[5-[2-(4-phenoxyphenyl)ethylsulfamoyl]thiophen-2-yl]methyl-[[3-(trifluoromethyl)phenyl]methyl]amino]acetic acid Chemical compound C=1C=CC(C(F)(F)F)=CC=1CN(CC(=O)O)CC(S1)=CC=C1S(=O)(=O)NCCC(C=C1)=CC=C1OC1=CC=CC=C1 QWOVDAMKKHZSLJ-UHFFFAOYSA-N 0.000 claims description 2
- WCXSXCMXAUTJFL-UHFFFAOYSA-N 2-[benzyl-[[4-(tridecanoylamino)phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C1=CC(NC(=O)CCCCCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CC1=CC=CC=C1 WCXSXCMXAUTJFL-UHFFFAOYSA-N 0.000 claims description 2
- FTIHOVWXUHDSKE-UHFFFAOYSA-N 2-[benzyl-[[4-[(4-hexoxybenzoyl)amino]phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C1=CC(OCCCCCC)=CC=C1C(=O)NC(C=C1)=CC=C1CN(C(=O)C(O)=O)CC1=CC=CC=C1 FTIHOVWXUHDSKE-UHFFFAOYSA-N 0.000 claims description 2
- ANHLFBREFORGGL-UHFFFAOYSA-N 2-[benzyl-[[4-[dodecyl(methyl)carbamoyl]phenyl]methyl]amino]-2-oxoacetic acid Chemical compound C1=CC(C(=O)N(C)CCCCCCCCCCCC)=CC=C1CN(C(=O)C(O)=O)CC1=CC=CC=C1 ANHLFBREFORGGL-UHFFFAOYSA-N 0.000 claims description 2
- UXFQFBNBSPQBJW-UHFFFAOYSA-N 2-amino-2-methylpropane-1,3-diol Chemical class OCC(N)(C)CO UXFQFBNBSPQBJW-UHFFFAOYSA-N 0.000 claims description 2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Epidemiology (AREA)
- Vascular Medicine (AREA)
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- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention is related to the use of substituted methylene amide derivatives of Formula (I) for the treatment and/or prevention of cardiovascular disorders such as coronary obstruction and heart failure. In particular, the present invention is related to the use of substituted methylene amide derivatives of Formula (I) in particular for the treatment and/or prevention of endothelial dysfunction in heart failure.
Description
Technical field
Cardiovascular disease such as arteria coronaria block and heart failure particularly prevents and/or treats the purposes in the endothelial function disturbance in the heart failure preventing and/or treating to the present invention relates to the methylene amide derivatives shown in the general formula (I).The peripheral blood vessel of chemical compound of the present invention in chronic heart failure is particularly useful on shrinking and increasing.
Background technology
Although closely recent decades, there was significant progress in cardiology and department of cardiac surgery field,, heart failure still causes high M ﹠ M.
Nearly 5,000,000 Americans suffer from heart failure, in over-65s the elderly sickness rate be 10/1000ths (Jessup et al., 2005, N.EngL J.Med, 348 (20), 2007-2018).
In the past decade, the hospitalization of heart failure increase by 159% (Jessup et aL, 2003, the same).The reason that sickness rate so increases progressively is that the aging of population, heart disease such as acute myocardial infarction and non-heart disease such as treatment for cancer are improved.
Heart failure is the result that S﹠S that cardiac dysfunction causes influences each other.Its development of root According and progressive character, brainstrust with heart failure from heart failure take place high-risk to carrying out property of heart textural anomaly to latter stage symptom procedure definition be four-stage (1-4) (Hunt et aL, 2001, J.Jim.Coll.Cardiol., 38,2101-13).
Heart failure mainly is defined as the unable blood of penetrating of heart, can not provide enough perfusions to the peripheral organ.Heart failure not only influences cardiac muscle, and peripheral circulation is produced a lot of harmful effects, especially when heart failure increases with the Peripheral resistance that is secondary to the peripheral blood vessel contraction.Vasoconstriction is formed by different factors, main influence " non-important " internal organs, and as skin, intestinal and skeletal muscle, the perfusion of " important " internal organs such as brain or heart when reducing to keep cardiac output.But this initial adaptation mechanism can increase cardiac afterload (to the drag of ventricular systole) and cardiac work chronically, thereby increases the weight of contraction abnormalities, impels the compensatory heart failure to change to non-compensatory heart failure.The long-term damage of cardiac activity or reduction cause the generation of chronic heart failure (CHF).
Endothelium is made of the cell monolayer that is positioned at blood and blood vessel wall interface.Endothelium plays an important role on control people blood vessel tensity and adjusting platelet and leukocyte function by the nitrous oxide (NO) that discharges endothelium derivation.
Usually unusual by endothelial function is evaluated in the endothelial NO generation minimizing of blood flow response, contraction increases Peripheral resistance thereby endothelial function strengthens peripheral blood vessel unusually.Experiment and clinical early stage cardiovascular disease comprise long-term heart failure, show that all endothelial function is unusual.
NO plays main effect on control vascular tone, regional blood flow and blood pressure.Endotheliocyte discharges NO constantly by activating endothelial NO synthetic (eNOS).
Blood flow is that the major physiological that NO continues to discharge is stimulated, and causes the vasodilation (FMD) of blood flow dependency vasodilation or blood flow mediation.ENOS by the blood flow mediation activates the vasodilation that reaches the blood flow mediation.The influence of create antagonism vasoconstrictive factor such as sympathetic nervous system or vasoconstrictor peptide Angiotensin II or the Endothelin of composing type NO, now generally be considered to circulate in exist the strong vasodilator effect of persistency relevant.
The physiological action of NO is not limited to vasodilation.In fact, the NO of endothelium derivation also by platelet increasing cGMP become platelet aggregation and adherent effective inhibitor (Radomski etc., 1987, Br.J.Pharmacol., 92,639-646).When NO produces with physiological concentration, also show effective anti-inflammatory effect, particularly suppress the adhesion of leukocyte and endotheliocyte.
The generation of endothelial NO reduces, and causes that peripheral blood vessel shrinks and platelet aggregation, causes secondary vasospasm and thrombotic dangerous increasing respectively.In addition, set NO leukocyte activation and adhesion are had depression effect, then endothelial function disturbance is considered to one of triggering factor of local vascular inflammatory response, the latter cause atherosclerotic generation (Ross, 1993, Nature, 362:801-809).
Some clinical datas focus on the effect that endothelial function disturbance, NO produce impaired or eNOS gene mutation or cardiovascular disease defective recently.Be subjected to the support of some epidemiological studies about the hypothesis that concerns between endothelial function disturbance and the atherosclerosis, these studies show that early stage endothelial function disturbance is the early warning (Suwaidi etc. of atherosclerosis and coronary heart disease development, 2000, Circulation, 101,948-954; Schachinger etc., 2000, Circulation, 101,1899-1906; Perticone etc., 2001, Circulation, 104,191-196).Nearest clinical research report, the eNOS gene mutation is shortened NOS in the intravital half-life of patient, does not have deterioration (McNamara etc., 2003 of incident existence with heart failure patient, Circulation, 107,1598-1602), with the consistent (Scherrer-Crosbie etc. of data of eNOS deficient mice, 2001, Circulation, 104,1286-1291).
The methylene amide derivatives of the replacement shown in the mutual-through type (I) as Protein Tyrosine Phosphatases (PTP) inhibitor particularly Protein Tyrosine Phosphatases 1B (PTP1B) inhibitor study, be used for the treatment of the treatment (WO 03/064376) of metabolic disease of insulin patience or hyperglycemia mediation.
Protein Tyrosine Phosphatases (PTP) plays an important role on the adjusting protein phosphorylation, represents the kinases counter pair.PTP regulates signal transduction path behind the interaction of insulin and its receptor and the receptor by the dephosphorylation of catalysis insulin receptor kinase cell substrate.The inhibitor of PTP-1B is known (Moller etc., 2000, Current Opinion in Drug Discovery ﹠amp on treating diabetes; Development3 (5), 527-540).
Several heart failure therapy agent have been developed, as beta blocker, diuretic, angiotensin receptor blocker, angiotensin converting enzyme (ACE) inhibitor (Chin etc., 2001, Current Opinion inInvestigational drugs, 2 (7), 923-928).
But multifactor and the carrying out property character of heart failure is for providing multiple probability to the treatment intervention of heart failure with to the demand of the new therapeutic modality of heart failure, especially for chronic heart failure.
Clinical evidence prompting listed above, the increase of Peripheral resistance partly is that the nitrous oxide (NO) that particularly persistent blood flow causes discharges owing to weakening that vasodilation influences.
Therefore, the impaired heart failure that may impel that periphery NO produces increases the weight of, and the generation of NO can be brought into play useful effect when medicine was got involved with the recovery heart failure in this disease.
Summary of the invention
The present invention relates to the methylene amide derivatives shown in the general formula (I)
Cardiovascular disease such as arteria coronaria block and heart failure particularly treats and/or prevents the purposes in the endothelial function disturbance in the chronic heart failure treating and/or preventing.The peripheral blood vessel of chemical compound of the present invention in chronic heart failure shrinks particularly useful.
Detailed Description Of The Invention
Following paragraph provides the definition of the various chemical groups that constitute The compounds of this invention, and they as one man are applied in whole description and claims, unless special in addition definition of setting forth provides wideer definition.
" PTP " is Protein Tyrosine Phosphatases, comprises for example PTP1B, TC-PTP, PTP-β, DEP-1, LAR, SHP-1, SHP-2, GLEPP-1, PTP-κ, PTP-μ, VHR, hVH5, LMW-PTP, PTEN.
" C
1-C
12Alkyl " or " C
1-C
15Alkyl " refer to have the straight or branched univalent alkyl of 1-12 or 1-15 carbon atom.Following group can be lifted in this term is example: methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, n-hexyl, n-octyl, n-nonyl, dodecyl, tridecyl, pentadecyl, n-pentyl etc., and their straight or branched form.
" aryl " refers to the unsaturated aromatic carbon ring of 6-14 carbon atom, has a monocycle (as phenyl) or a plurality of fused rings (as naphthyl).Preferable aryl comprises phenyl, naphthyl, phenanthryl etc.
" C
1-C
12Alkylaryl " refer to the to have aryl substituent C of (comprising phenyl, phenethyl etc.)
1-C
12Alkyl.
" heteroaryl " refers to bicyclic heteroaryl or bicyclo-or three ring condensed ring heteroaryls.The object lesson of heteroaryl comprises the pyridine radicals that can replace arbitrarily, pyrrole radicals, furyl, thienyl, imidazole radicals oxazolyl isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2, the 3-triazolyl, 1,2, the 4-triazolyl, 1,2,3-oxadiazole base, 1,2,4-oxadiazole base, 1,2,5-oxadiazole base, 1,3,4-oxadiazole base, 1,3, the 4-triazine radical, 1,2, the 3-triazine radical, benzofuranyl, [2, the 3-dihydro] benzofuranyl, isobenzofuran-base, benzothienyl, the benzotriazole base, isobenzo-thienyl, indyl, isoindolyl, the 3H-indyl, benzimidazolyl, imidazo [1,2-a] pyridine radicals, benzothiazolyl benzoxazolyl, quinolizinyl, quinazolyl, 2, the 3-phthalazinyl, quinoxalinyl, the cinnolines base, the naphthyridine base, pyrido [3,4-b] pyridine radicals, pyrido [3,2-b] pyridine radicals, pyrido [4,3-b] pyridine radicals, quinolyl, isoquinolyl, tetrazole radical, 5,6,7, the 8-tetrahydric quinoline group, 5,6,7, the 8-tetrahydro isoquinolyl, fast quinoline base, pteridine radicals, carbazyl, xanthyl or benzoquinoline base.
" C
1-C
12Miscellaneous alkyl aryl " refer to have the substituent C of heteroaryl
1-C
12Alkyl comprises 2-furyl methyl, 2-thienyl methyl, 2-(1H-indol-3-yl) ethyl etc.
" alkenyl " refers to have 2-6 carbon atom and reaches the alkenyl at 1-2 the unsaturated position of thiazolinyl at least.Preferable alkenyl comprises vinyl (CH=CH
2), n-2-acrylic (pi-allyl ,-CH
2CH=CH
2) etc.
" alkynyl " refers to have 2-18 carbon atom and reaches the alkynyl at 1-2 the unsaturated position of alkynyl, for example acetenyl (CH ≡ CH), propinyl (CH at least
2CH ≡ CH) or-CH ≡ CH (C
1-C
16) alkyl etc.
" acyl group " refers to group-C (O) R, and wherein R comprises " C
1-C
12Alkyl ", " aryl ", " heteroaryl ", " C
1-C
12Alkylaryl ", " C
1-C
12Miscellaneous alkyl aryl ".
" acyloxy " refers to group-OC (O) R, and wherein R comprises " C
1-C
12Alkyl ", " aryl ", " heteroaryl ", " C
1-C
12Alkylaryl ", " C
1-C
12Miscellaneous alkyl aryl ".
" alkoxyl " refers to group-O-R, and wherein R comprises " C
1-C
12Alkyl " or " aryl " or " heteroaryl " or " C
1-C
12Alkylaryl " or " C
1-C
12Miscellaneous alkyl aryl ".Preferable alkoxyl comprises for example methoxyl group, ethyoxyl, phenoxy group etc.
" alkoxy carbonyl " refers to group-C (O) OR, and wherein R comprises " C
1-C
12Alkyl " or " aryl " or " heteroaryl " or " C
1-C
12Alkylaryl " or " C
1-C
12Miscellaneous alkyl aryl ".
" amino carbonyl " refers to group-C (O) NRR ', and wherein R, R ' comprise " hydrogen " or " C independently
1-C
12Alkyl " or " aryl " or " heteroaryl " or " C
1-C
12Alkylaryl " or " C
1-C
12Miscellaneous alkyl aryl ".
" acyl amino " refers to group-NR (CO) R ', and wherein R, R ' comprise " hydrogen " or " C independently
1-C
12Alkyl " or " aryl " or " heteroaryl " or " C
1-C
12Alkylaryl " or " C
1-C
12Miscellaneous alkyl aryl ".
" halogen " refers to fluorine, chlorine, bromine and iodine atom.
" replacement or unsubstituted ": unless limit about substituent definition out of the ordinary, above-mentioned group, 1-5 the substituent group that can randomly be selected from following group as " alkyl ", " alkenyl ", " alkynyl ", " aryl " and groups such as " heteroaryls " replaces: " C
1-C
6Alkyl ", " C
2-C
6Alkenyl ", " C
2-C
6Alkynyl ", " cycloalkyl ", " Heterocyclylalkyl ", " C
1-C
6Alkylaryl ", " C
1-C
6Miscellaneous alkyl aryl ", " C
1-C
6Alkyl-cycloalkyl ", " C
1-C
6The alkyl heterocycle alkyl ", " amino ", " ammonium ", " acyl group ", " acyloxy ", " acylamino-", " amino carbonyl ", " alkoxy carbonyl ", " urea groups ", " aryl ", " carbamate groups ", " heteroaryl ", " sulfinyl ", " sulfonyl ", " alkoxyl ", " sulfane base ", " halogen ", " carboxyl ", " trihalomethyl group ", " cyano group ", " hydroxyl ", " sulfydryl ", " nitro ", or the like.Perhaps; described replacement also can comprise following situation: contiguous substituent group experience ring closure; when particularly relating to contiguous function substituent group, thereby form for example lactams, lactone, cyclic anhydride, also can for example form acetal, sulfo-acetal, aminal by closed loop in order to obtain blocking group.
" sulfonyl " refers to group " SO
2-R ", wherein R is selected from H, " aryl ", " heteroaryl ", " C
1-C
12Alkyl ", " C that replaced by halogen
1-C
12Alkyl " as-SO
2-CF
3Group, " C
1-C
12Alkylaryl " or " C
1-C
12Miscellaneous alkyl aryl ".
" sulfinyl " refers to group " S (O)-R ", and wherein R is selected from H, " C
1-C
12Alkyl ", " C that replaced by halogen
1-C
12Alkyl " as-SO-CF
3Group, " aryl ", " heteroaryl ", " C
1-C
12Alkylaryl " or " C
1-C
12Miscellaneous alkyl aryl ".
" thio alkoxy " refers to group-S-R, and wherein R comprises " C
1-C
12Alkyl " or " aryl " or " heteroaryl " or " C
1-C
12Alkylaryl " or " C
1-C
12Miscellaneous alkyl aryl ".Preferable thio alkoxy comprises sulfo-methoxyl group, thio ethoxy etc.
" resistance arteries " refers to the tremulous pulse of diameter enough little (＜300 μ m), and for blood vessel, such diameter can influence local resistance and the adjusting thereof to blood flow significantly.Therefore the main Peripheral resistance of blood flow is provided by resistance arteries, in the control of the blood pressure of major organs system and blood flow with regulate very important.
Term " heart failure " comprised such as the differentiation of description such as Jessup (2003) and each stage of progress.It for example comprises that cardiac structure is unusual, relaxing period heart failure and systole heart failure.
" pharmaceutically acceptable salt or complex " refers to the salt or the complex of following concrete general formula (I) chemical compound.The example of these salt includes, but is not limited to general formula (I) chemical compound and inorganic base hydroxide, carbonate or the bicarbonate as the metal cation that is selected from alkali metal (sodium, potassium or lithium), alkaline-earth metal (as calcium or magnesium), or the base addition salts that forms with organic base such as organic primary, second month in a season or reactive tertiary amine.Derived from methylamine, dimethylamine, trimethylamine, ethamine, diethylamine, triethylamine, morpholine, N-methyl D-glucamine, N, the amine salt of N '-two (phenyl methyl)-1, tromethane, ethanolamine, diethanolamine, ethylenediamine, N-methylmorpholine, procaine, piperidines, piperazine etc. is considered within the scope of the invention.
Also comprise and mineral acid (example hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, nitric acid etc.) or the acid-addition salts that forms with organic acid (as acetic acid, oxalic acid, tartaric acid, succinic acid, malic acid, fumaric acid, maleic acid, ascorbic acid, benzoic acid, tannic acid, pamoic acid, alginic acid, polyglutamic acid, LOMAR PWA EINECS 246-676-2, naphthalenedisulfonic acid and polygalacturonic acid).
" pharmaceutical active derivant " can directly or indirectly provide this description described active any chemical compound after showing and giving the receptor.Term " indirectly " also comprises the prodrug that can be converted into the pharmaceutically active form through endogenous enzyme or metabolism.Described prodrug is made up of active pharmaceutical compounds itself and chemical masked radical.
" enantiomeric excess " (ee) refers to promptly relate to the synthetic of non-racemization parent material and/or reagent or comprise the synthetic product that is obtained of at least a enantioselectivity step by asymmetric synthesis, obtains excessive a kind of enantiomer at least about 52%ee with this.Under the situation that lacks asymmetric synthesis, the corresponding ester of substituted methylene amide shown in general formula (I), what obtain usually is racemic product, however they also have PTP and suppress active.
Described structural formula also comprises its tautomer, geometric isomer, as the optical activity form and the racemic compound thereof of enantiomer, diastereomer, and their pharmaceutically acceptable salt.The pharmaceutically acceptable salt of preferable general formula (I) chemical compound is the base addition salts that carbonate, bicarbonate or the hydroxide reaction of general formula (I) chemical compound and pharmaceutically acceptable alkali such as N-methyl D-glucamine, tromethane, sodium, potassium or calcium forms.
Methylene amide derivatives of the present invention is a chemical compound shown in the general formula (I):
Chemical compound shown in the general formula (I) also comprises its geometric isomer, optical activity form (comprising enantiomer, diastereomer) and racemic compound thereof, and their pharmaceutically acceptable salt and pharmaceutical active derivant.
Substituent R in the general formula (I)
1, R
2a, R
2bBe defined as follows with Cy:
R
1Be selected from and replace or unsubstituted (C
1-C
15) alkyl, replacement or unsubstituted (C
1-C
12) alkyl, replacement or unsubstituted (C
1-C
6) alkyl, replacement or unsubstituted (C
2-C
12) alkenyl, replacement or unsubstituted (C
2-C
12) alkynyl, replacement or unsubstituted aryl, replacement or unsubstituted heteroaryl, replacement or unsubstituted (3-8 unit) cycloalkyl or Heterocyclylalkyl, replacement or unsubstituted (C
1-C
12) alkylaryl or replacement or unsubstituted (C
1-C
12) miscellaneous alkyl aryl, replacement or unsubstituted (C
2-C
12) alkenyl-aryl/-heteroaryl, replacement or unsubstituted (C
2-C
12) alkynyl-aryl/-heteroaryl;
R
2aAnd R
2bBe selected from H or replacement or unsubstituted (C independently of one another
1-C
12) alkyl, R
2aAnd R
2bThe preferable H that is;
Cy is selected from D and E;
D is selected from the thienyl of replacement and the phenyl of replacement, and wherein substituent group is selected from phenyl, oxadiazole base or is selected from-NH-CO-R
3,-SO
2-NR
3R
3 'With-CO-NR
3R
3 'One or two group, R wherein
3And R
3 'Be selected from H, replacement or unsubstituted (C independently of one another
1-C
15) alkyl, replacement or unsubstituted (C
2-C
12) alkenyl, replacement or unsubstituted (C
2-C
12) alkynyl, replacement or unsubstituted aryl, replacement or unsubstituted heteroaryl, replacement or unsubstituted (3-8 unit) cycloalkyl or replacement or unsubstituted Heterocyclylalkyl, replacement or unsubstituted (C
1-C
12) alkyl-aryl/-heteroaryl, replacement or unsubstituted (C
2-C
12) alkenyl-aryl/-heteroaryl, replacement or unsubstituted (C
2-C
12) alkynyl-aryl/-heteroaryl;
E is selected from aryl, heteroaryl, (3-8 unit)-cycloalkyl and Heterocyclylalkyl, wherein aryl, heteroaryl, (3-8 unit)-cycloalkyl and the Heterocyclylalkyl (C that can be optionally substituted
2-C
18) alkynyl substituted;
Such aryl or heteroaryl comprise phenyl, naphthyl, phenanthryl, pyrrole radicals, furyl, thienyl, imidazole radicals, pyridine radicals oxazolyl isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2, the 3-triazolyl, 1,2, the 4-triazolyl, 1,2,3-oxadiazole base, benzo (1,2,5)-oxadiazole bases, 1,2,4-oxadiazole base, 1,2,5-oxadiazole base, 1,3,4-oxadiazole base, tetrazole radical, 1,3, the 4-triazine radical, 1,2, the 3-triazine radical, the benzo pyrimidine radicals, benzofuranyl, [2, the 3-dihydro] benzofuranyl, isobenzofuran-base, benzothienyl, the benzotriazole base, isobenzo-thienyl, indyl, isoindolyl, the 3H-indyl, benzimidazolyl, benzothiazolyl benzoxazolyl, pyridazinyl, pyrimidine radicals, quinolizinyl, quinazolyl, the 2 base, quinoxalinyl, the cinnolines base, 1, the 5-phthalazinyl, quinolyl, isoquinolyl, tetrazole radical, 5,6,7, the 8-tetrahydric quinoline group, 5,6,7, the 8-tetrahydro isoquinolyl, fast quinoline base, pteridine radicals, xanthyl, the benzoquinoline base, oxa-penta cyclic group (oxolanyl), pyrrolidinyl, pyrazolidinyl, 2H-benzo [d] 1, the 3-dioxa cyclopentenyl (2H-benzo[d] 1,3-dioxolenyl), indanyl, imidazolidinyl, 1,2,4-oxadiazole alkyl (1,2,4-oxadiazolidinyl), 1,2,5-oxadiazole alkyl, 1,3,4-oxadiazole alkyl Huo isoxazole alkyl.
In a preferred embodiment, R
2aAnd R
2bBe H.
In another preferred embodiment of the present invention, R
1Be A, wherein A is selected from and replaces or unsubstituted aryl, replacement or unsubstituted heteroaryl, replacement or unsubstituted (3-8 unit) heterocyclic aryl, and replaces or unsubstituted (3-8 unit) cycloalkyl, particularly replaces or unsubstituted phenyl.
In a further preferred embodiment, R
1Be general formula-CH
2-A or-CH
2-CH
2Group shown in the-A, wherein A is selected from and replaces or unsubstituted aryl, replacement or unsubstituted heteroaryl, replacement or unsubstituted (3-8 unit) heterocyclic aryl, and replaces or unsubstituted (3-8 unit) cycloalkyl.
Particularly, A can be phenyl, pyridine radicals, phendioxin, 3-dioxa cyclopentenyl (benzo-1,3-dioxolenyl), xenyl, naphthyl, quinoxalinyl, thiazolyl, thienyl, furyl or piperidyl, can randomly be selected from following group 1 or 2 groups and be replaced: cyano group, halogen, NO
2, (C
1-C
6) alkoxyl, aryloxy group or heteroaryloxy, (C
1-C
6) thio alkoxy, (C
1-C
12) alkyl, can be by halogenated (C arbitrarily
1-C
12) alkyl, (C
2-C
12) alkenyl, (C
2-C
12) alkynyl, aryl, heteroaryl, (3-8 unit) cycloalkyl or Heterocyclylalkyl, (C
1-C
12) alkylaryl or heteroaryl, (C
2-C
12) alkenyl aryl or heteroaryl, (C
2-C
12) alkynyl aryl or heteroaryl ,-COR
3,-COOR
3,-CO-NR
3R
3 ', NHCOR
3, R wherein
3Be (C
1-C
12) alkyl or (C
2-C
12) alkenyl ,-SOR
3,-SO
2R
3,-SO
2NR
3R
3', R wherein
3, R
3 'Be selected from H, straight or branched (C independently of one another
1-C
12) alkyl, (C
2-C
12) alkenyl, (C
2-C
12) alkynyl, aryl, heteroaryl, (3-8 unit) cycloalkyl or Heterocyclylalkyl.
According to an embodiment, Cy is D.
According to another embodiment, R
3 'Be H, R
3Be selected from xenyl ethyl, dodecyl, octyl group, 4-amyl group benzyl, 4-phenoxy group phenethyl, ethylthiophene-2-base, pentadecyl, tridecyl, hexyloxy phenyl, (2-ethyl)-hexyl.
According to another embodiment, Cy is E.
According to also having an embodiment, Cy is E, and wherein E is selected from phenyl, pyridine radicals, naphthyl and benzofuranyl, and phenyl, pyridine radicals, naphthyl and benzofuranyl are by B-R
4Replace, wherein B is an acetenyl, R
4For replacing or unsubstituted (C
6-C
16) alkyl, replacement or unsubstituted (3-8 unit) cycloalkyl, replacement or unsubstituted (C
1-C
12) alkyl-(3-8 unit) cycloalkyl, replacement or unsubstituted phenyl or replacement or unsubstituted (C
1-C
12) alkyl phenyl.
More particularly, E is by B-R
4The phenyl that replaces, wherein B is an acetenyl, R
4For replacing or unsubstituted (C
6-C
16) alkyl.
According to another embodiment, R
2aAnd R
2bBe H, R
1For-CH
2-A or-CH
2-CH
2-A, wherein A is phenyl or thienyl, can choose wantonly by cyano, halogen, methoxyl group, hydroxyl, phenoxy group ,-NO
2, trifluoromethyl replaces, and Cy is D, wherein D is selected from thienyl, phenyl and xenyl; Wherein thienyl, phenyl and xenyl quilt-SO
2R
3,-CO-NR
3R
3 'Replace, wherein R
3 'Be H, R
3Be (C
7-C
12) alkyl, particularly (C
8-C
12) alkyl, more particularly be dodecyl.
According to also having an embodiment, R
2aAnd R
2bBe H, R
1For-CH
2-A or-CH
2-CH
2-A, wherein A is phenyl or thienyl, can choose wantonly by cyano, halogen, methoxyl group, hydroxyl, phenoxy group ,-NO
2, trifluoromethyl replaces, and Cy is D, wherein D is selected from thienyl, phenyl and xenyl; Wherein thienyl, phenyl and xenyl quilt-SO
2R
3,-CO-NR
3R
3 'Replace, wherein R
3 'Be H, R
3Be (C
7-C
15) alkyl, particularly (C
8-C
15) alkyl, more particularly be dodecyl.
According to also having an embodiment, R
2aAnd R
2bBe H, R
1Be selected from phenyl, benzyl, phenethyl, 1-methyl-benzyl, can be by (C
1-C
6) the alkyl or cycloalkyl replacement; Cy is D, and wherein D is selected from phenyl and xenyl, and wherein phenyl and xenyl are selected from-NH-CO-R
3,-CO-NH-R
3Group replace, and by R
3Replace De oxadiazole base, wherein R
3Be (C
7-C
15) alkyl, particularly (C
8-C
15) alkyl, more particularly be dodecyl.
Preferred chemical compound is a chemical compound shown in the general formula (I '),
Wherein
R
1Be selected from phenyl, benzyl, phenethyl, 1-methyl-benzyl, can be by (C
1-C
6) the alkyl or cycloalkyl replacement; Cy is D, and wherein D is selected from phenyl and xenyl; Phenyl and xenyl can be selected from-NH-CO-R
3,-CO-NH-R
3And R
3The substituent group that replaces De oxadiazole base replaces, wherein R
3Be (C
7-C
15) alkyl, particularly (C
8-C
15) alkyl, more especially dodecyl.
Chemical compound of the present invention is particularly including following chemical compound:
(benzyl 4-[dodecyl amino] and carbonyl } benzyl } amino) (oxo) acetic acid;
Oxo 4-[(pentadecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } acetic acid;
(benzyl 4-[(pentadecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
(benzyl 4-[(tridecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
[benzyl (4-{[dodecyl (methyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
(4-{[dodecyl (methyl) amino] carbonyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
([1-(tert-butoxycarbonyl)-4-piperidyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
({ [1-(tert-butoxycarbonyl)-4-piperidyl] methyl } { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
Oxo { [4-(tridecanoyl amino) benzyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
[benzyl (4-{[4-(hexyloxy) benzoyl] amino } benzyl) amino] (oxo) acetic acid;
Oxo { [4-trifluoromethyl] benzyl } [4-(10-endecatylene acyl amino) benzyl] amino } acetic acid;
Oxo 4-[(9E)-9-tetradecene acyl amino] benzyl } [4-(trifluoromethyl) benzyl] amino } acetic acid;
{ benzyl [4-(tridecanoyl amino) benzyl] amino } (oxo) acetic acid;
4-[(2-hydroxyl dodecyl) and amino] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (the 1-[(4-methoxyphenyl) sulfonyl]-the 4-piperidyl } methyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-carboxyl-1-phenylethyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-methoxyl group-1-Methylethyl) amino] (oxo) acetic acid;
(the 4-bromine 4-[(dodecyl amino) and carbonyl] benzyl } anilino-) (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } anilino-) (oxo) acetic acid;
([2-(3-chlorphenyl) ethyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(3-methoxyphenyl) ethyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(d, 1)-trans-2-phenycyclopropyl] amino } (oxo) acetic acid;
([(d, 1)-trans-2-benzyloxy] cyclopenta) { 4-[((dodecyl amino) carbonyl) benzyl]-amino } (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl }-4-phenoxybenzamine base) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (1,2,3,4-tetrahydrochysene-1-naphthyl) amino] (oxo) acetic acid;
((1-benzyl-4-piperidyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(4-Phenoxyphenyl) ethyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(2-Phenoxyphenyl) ethyl] amino } (oxo) acetic acid;
((2-[1,1 '-xenyl]-4-base ethyl) and 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
(([1,1 '-xenyl]-3-ylmethyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
(3-(benzyloxy) 4-[(dodecyl amino) and carbonyl] benzyl } benzyl) anilino-) (oxo) acetic acid;
([4-(benzyloxy amino) benzyl] { 4-[((dodecyl amino) carbonyl) benzyl] amino } (oxo) acetic acid;
N-(carboxyl carbonyl)-N-{4-[(dodecyl amino) carbonyl] benzyl }-3-phenyl-β-aniline;
4-[(dodecyl amino) and carbonyl] benzyl } [4-(1,2,3-thiadiazoles-4-yl) benzyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-phenylbenzyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (1-phenylethyl) amino] (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [1-(1-naphthyl) ethyl] amino } (oxo) acetic acid;
(benzyl 3-[(dodecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
3-[(dodecyl amino) and carbonyl] benzyl } [4-(methyl sulphonyl) benzyl] amino } (oxo) acetic acid;
((3-cyano group benzyl) { 3-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
3-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
[(4-benzyl chloride base) (3-{[(4-phenylbenzyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
Oxo { [4-({ [2-(2-thienyl) ethyl] amino } carbonyl) benzyl] [4-((trifluoromethyl) benzyl) amino] acetic acid;
Benzyl [(3 '-{ [(2,2-xenyl ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(3-cyano group benzyl) [(3 '-{ [(2,2-xenyl ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(4-benzyl chloride base) [3 '-{ [(2,2-xenyl ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
[(3 '-{ [(2,2-xenyl ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
((3-cyano group benzyl) { [3 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) [1,1 '-xenyl]-the 4-yl] methyl } amino) (oxo) acetic acid;
Oxo [3 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) [1,1 '-xenyl]-the 4-yl] methyl }-[4-(trifluoromethyl) benzyl] amino } acetic acid;
[(3-cyano group benzyl) (3 '-[(octyl group amino) carbonyl] [1,1 '-xenyl]-4-yl } methyl) amino] (oxo) acetic acid;
[(4-benzyl chloride base) (3 '-[(octyl group amino) carbonyl] [1,1 '-xenyl]-4-yl } methyl) amino] (oxo) acetic acid;
(3 '-[(octyl group amino) carbonyl] [1,1 '-xenyl]-4-yl } methyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(3-cyano group benzyl) [(3 '-{ [(3-phenyl propyl) amino] carbonyl } [1,1 '-xenyl]-the 4-yl] methyl } amino } (oxo) acetic acid;
[(3-cyano group benzyl) (3 '-[(dodecyl amino) carbonyl] [1,1 '-xenyl]-the 4-yl } methyl) amino] (oxo) acetic acid;
[(4-benzyl chloride base) (3 '-[(dodecyl amino) carbonyl] [1,1 '-xenyl]-the 4-yl } methyl) amino] (oxo) acetic acid;
(3 '-[(dodecyl amino) carbonyl] [1,1 '-xenyl]-the 4-yl } methyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Benzyl [(3 '-{ [(4-phenylbenzyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(3-cyano group benzyl) [3 '-{ [(4-phenylbenzyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(4-benzyl chloride base) [3 '-{ [(4-phenylbenzyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
Oxo [(3 '-{ [(4-phenylbenzyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
Oxo [(3 '-{ [(4-phenyl butyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
(3-cyano group benzyl) [(3 '-{ [(2- base ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(4-benzyl chloride base) [(3 '-{ [(2- base ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
[(3 '-{ [(2- base ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
((4-benzyl chloride base) { [3 '-({ [2-(4-methoxyphenyl) ethyl] amino } carbonyl) [1,1 '-xenyl]-the 4-yl] methyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-methoxy-benzyl) amino] (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } (4-methyl sulphonyl) benzyl } amino } (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (4-methoxy-benzyl) amino] (oxo) acetic acid;
3-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } { [6-(trifluoromethyl)-3-pyridine radicals] methyl } amino) (oxo) acetic acid;
4-[((carboxyl carbonyl) 3-[(dodecyl amino) and carbonyl] benzyl } amino) methyl] benzoic acid;
(3-[(dodecyl amino) and carbonyl] benzyl } 4-[hydroxyl (epoxy) amino] benzyl }-amino) (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (2-luorobenzyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (2-pyridylmethyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (3-thienyl methyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (4-hydroxybenzyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (4-phenoxy benzyl) amino] (oxo) acetic acid;
(3-[(dodecyl amino) and carbonyl] benzyl } { [6-(trifluoromethyl)-3-pyridine radicals] methyl }-amino) (oxo) acetic acid;
3-[((carboxyl carbonyl) 3-[(dodecyl amino) and carbonyl] benzyl } amino) methyl] benzoic acid;
5-[((carboxyl carbonyl) 3-[(dodecyl amino) and carbonyl] benzyl } amino) methyl]-2-thio phenyl carboxylic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } 4-[hydroxyl (epoxy) amino] benzyl }-amino) (oxo) acetic acid;
((1,3-benzo dioxole-5-ylmethyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-luorobenzyl) amino] (oxo) acetic acid;
[4-[((dodecyl amino) and carbonyl) benzyl] (4-phenoxy benzyl) amino } (oxo) acetic acid;
4-[((carboxyl carbonyl) 4-[(dodecyl amino) and carbonyl] benzyl } amino) methyl] benzoic acid;
5-[((carboxyl carbonyl) 4-[(dodecyl amino) and carbonyl] benzyl } amino) methyl]-2-thio phenyl carboxylic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (2-thienyl methyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (isopropyl) amino] (oxo) acetic acid;
(3, the 5-dichloro benzyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[(3, the 5-dichloro benzyl) (4-{[(3,3-xenyl propyl group) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
[(4-{[(2-[1,1 '-xenyl]-4-base ethyl) amino] carbonyl } benzyl) (3, the 5-dichloro benzyl)-amino] (oxo) acetic acid;
[(1,3-benzo dioxole-5-ylmethyl) (4-{[(2-[1,1 '-xenyl]-4-base ethyl)] amino] carbonyl benzyl] amino] (oxo) acetic acid;
(2,3-dihydro-1H-indenes-1-base 4-[(dodecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
{ 2,3-dihydro-1H-indenes-1-base [4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-pyridylmethyl) amino] (oxo) acetic acid;
([4-(dimethylamino) benzyl 4-[(dodecyl amino) and carbonyl] benzyl } amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (3-pyridylmethyl) amino] (oxo) acetic acid;
((4-cyano group benzyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (1,3-thiazoles-2-ylmethyl) amino] (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } { [2-(4-morpholinyl)-1,3-thiazoles-5-yl] methyl }-amino) (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (4-pyridylmethyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (3-pyridylmethyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (3-hydroxybenzyl) amino] (oxo) acetic acid;
((4-cyano group benzyl) { 3-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (1,3 thiazol-2-yl methyl) amino] (oxo) acetic acid;
(3-[(dodecyl amino) and carbonyl] benzyl } { [2-(4-morpholinyl)-1,3-thiazoles-5-yl] methyl } amino) (oxo) acetic acid;
((1,3-benzo dioxole-5-ylmethyl) { 3-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-thienyl methyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-pyridylmethyl) amino]] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (3-thienyl methyl) amino]] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-hydroxybenzyl) amino]] (oxo) acetic acid;
3-[((carboxyl carbonyl) 4-[(dodecyl amino) and carbonyl] benzyl } amino) methyl] benzoic acid;
[cyclopenta (5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) amino] (oxo) acetic acid;
[benzyl (5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) amino] (oxo) acetic acid;
((5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) 3-[[hydroxyl (epoxy) amino] and benzyl] amino } (oxo) acetic acid;
[(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) (4-methoxy-benzyl) amino] (oxo) acetic acid;
[(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) (2-luorobenzyl) amino] (oxo) acetic acid;
(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) [4-(methyl sulphonyl)-benzyl] amino } (oxo) acetic acid;
[(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) (4-phenoxy benzyl) amino] (oxo) acetic acid;
4-{[(carboxyl carbonyl) (5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) amino] methyl } benzoic acid;
((5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) { [6-(trifluoromethyl)-3-pyridine radicals] methyl } amino) (oxo) acetic acid;
(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
[(3-benzyl chloride base) (and 5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) amino] (oxo) acetic acid;
{ [(5-{[(3,3-xenyl propyl group) amino] sulfonyl }-2-thienyl) methyl] [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (3-benzyl chloride base) [(5-{[(3,3-xenyl propyl group) amino] sulfonyl }-2-thienyl) methyl] amino } (oxo) acetic acid;
Oxo { { [5-({ [2-(4-Phenoxyphenyl) ethyl] amino } sulfonyl)-2-thienyl] methyl } [3-(trifluoromethyl) benzyl] amino } acetic acid;
((3-benzyl chloride base) { [5-({ [2-(4-Phenoxyphenyl) ethyl] amino } sulfonyl)-2-thienyl] methyl } amino) (oxo) acetic acid;
[(5-{[(2-[1,1 '-xenyl]-4-base ethyl) amino] sulfonyl }-the 2-thienyl) methyl] [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
((1-[(cyclohexyl amino) carbonyl]-the 4-piperidyl } methyl) 4-[(dodecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
([(1-{[4-(dimethylamino) anilino-] carbonyl }-the 4-piperidyl) methyl] 4-[(dodecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(1-caproyl-4-piperidyl) methyl] amino } (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } { [1-(3-iodobenzene formoxyl)-4-piperidyl] methyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(1-{ (2E)-3-[3-(trifluoromethyl) phenyl]-the 2-acryloyl group }-the 4-piperidyl) methyl] amino } (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } { [1-(2-quinoxalinyl carbonyl)-4-piperidyl] methyl } amino) (oxo) acetic acid;
[(the 1-[(4-methoxyphenyl) sulfonyl]-the 4-piperidyl } methyl) (4-{[(4-phenoxy benzyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
[{ [1-(3-iodobenzene formoxyl)-4-piperidyl] methyl } (4-{[(4-phenoxy benzyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
Oxo (4-{[(4-phenoxy benzyl) amino] and carbonyl } benzyl) [(1-{ (2E)-3-[3-(trifluoromethyl) phenyl]-the 2-acryloyl group }-the 4-piperidyl) methyl] amino } acetic acid;
4-[(dodecyl amino) and carbonyl] phenyl } [2-(methoxycarbonyl) benzyl]-amino } (oxo) acetic acid;
[[4-([2-(1,1 '-xenyl-4 base) ethyl] amino } carbonyl)-the 2-bromobenzyl] (4-iodine benzyl) amino] (oxo) acetic acid;
[(2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) (4-iodine benzyl) amino] (oxo) acetic acid;
[2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } (4-iodine benzyl) amino] (oxo) acetic acid;
[(2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) (4-iodine benzyl) amino] (oxo) acetic acid;
((4-iodine benzyl) { [4 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl)-1,1 '-xenyl-4 base] methyl } amino) (oxo) acetic acid;
[2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
[4-([2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-the 2-bromobenzyl] [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
(2-bromo-4-{[(4-phenylbenzyl) amino] and carbonyl } benzyl) [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
[2,6-two bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
[4-([2-(1,1 '-xenyl-4 base) ethyl] amino } carbonyl)-2,6 dibromo-benzyls] [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-phenylbenzyls) amino] and carbonyl } benzyl) [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
([(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] [4 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
(4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
(2-bromo-4-{[(4-amyl group benzyl) amino] and carbonyl } benzyl) [2-(trifluoromethoxy)-benzyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-amyl group benzyls) amino] and carbonyl } benzyl) [2-(trifluoromethoxy)-benzyl] amino } (oxo) acetic acid;
Oxo [4 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl)-1,1 '-xenyl-4-yl] methyl }-[2-(trifluoromethoxy) benzyl] amino } acetic acid;
(4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [2-(trifluoromethoxy)-benzyl] amino } (oxo) acetic acid;
[[2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] (3-methoxyl group-benzyl) amino] (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] (3-phenoxy benzyl) amino] (oxo) acetic acid;
[(2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) (3-phenoxy benzyl) amino] (oxo) acetic acid;
[[2,6-two bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] (3-phenoxy benzyl) amino] (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2,6-dibromo-benzyl] (3-phenoxy benzyl) amino] (oxo) acetic acid;
[(2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) (3-phenoxy benzyl) amino] (oxo) acetic acid;
[2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } (3-phenoxy benzyl)-amino] (oxo) acetic acid;
Oxo ((3-phenoxy benzyl) { [4 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl)-1,1 '-xenyl-4-yl] methyl } amino) acetic acid;
Oxo [[(4 '-{ [(4-amyl group benzyl) amino] carbonyl }-1,1 '-xenyl-4-yl) methyl] (3-phenoxy benzyl) amino] acetic acid;
[(4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) (3-phenoxy benzyl) amino] (oxo) acetic acid;
[[2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] (2-iodine benzyl) amino] (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] (2-iodine benzyl) amino] (oxo) acetic acid;
[(2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) (2-iodine benzyl) amino] (oxo) acetic acid;
[2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } (2-iodine benzyl) amino] (oxo) acetic acid;
([2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] { [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
([4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] { [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
((2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
((2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino] (oxo) acetic acid;
(2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
([4-([2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2, the 6-dibromo-benzyl] [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
((2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
(2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino] (oxo) acetic acid;
((4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] (1,1 '-xenyl-2-ylmethyl) amino] (oxo) acetic acid;
[(1,1 '-xenyl-2-ylmethyl) (2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
((1,1 '-xenyl-2-ylmethyl) { 2-bromo-4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
{ (1,1 '-xenyl-2-ylmethyl) [2,6-two bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] amino } (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2,6-dibromo-benzyl] (1,1 '-xenyl-2-ylmethyl) amino] (oxo) acetic acid;
[(1,1 '-xenyl-2-ylmethyl) (2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
((1,1 '-xenyl-2-ylmethyl) { 2,6-two bromo-4-[(dodecyl amino) carbonyl] benzyl }-amino) (oxo) acetic acid;
(2-bromo-4-{[(4-amyl group benzyl) amino] and carbonyl } benzyl) [4-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-amyl group benzyls) amino] and carbonyl } benzyl) [4-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
(2-bromo-4-{[(4-amyl group benzyl) amino] and carbonyl } benzyl) [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-amyl group benzyls) amino] and carbonyl } benzyl) [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
(4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
[[2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] (4-phenoxy benzyl) amino] (oxo) acetic acid;
[[4-([2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-the 2-bromobenzyl] (4-phenoxy benzyl) amino] (oxo) acetic acid;
[(2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) (4-phenoxy benzyl) amino] (oxo) acetic acid;
[2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } (4-phenoxy benzyl) amino] (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2,6-dibromo-benzyl] (4-phenoxy benzyl) amino] (oxo) acetic acid;
[(2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) (4-phenoxy benzyl) amino] (oxo) acetic acid;
{ [4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] [4-(trifluoromethyl) benzylamino] (oxo) acetic acid;
(2-bromo-4-{[(4-amyl group benzyl) amino] and carbonyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-amyl group benzyls) amino] and carbonyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo [(4 '-{ [(4-amyl group benzyl) amino] carbonyl }-1,1 '-xenyl-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo [(4 '-{ [(4-amyl group benzyl) amino] carbonyl }-1,1 '-xenyl-4-yl) methyl] [3-(trifluoromethyl) benzyl] amino } acetic acid;
{ (4-dibenzo [b, d] furan-4-base benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-dibenzo [b, d] furan-4-base benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
(4-[(dodecyl amino) and carbonyl] benzyl } 1-[4-(trifluoromethyl) phenyl] and ethyl } amino) (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } 1-[4-(trifluoromethyl) phenyl] and ethyl } amino) (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
(4 '-[(octyl group amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { (4-14-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } acetic acid;
{ (4-12-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) phenyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-methoxyphenyl) amino] (oxo) acetic acid;
((1,2-xenyl ethyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
N-(carboxyl carbonyl)-N-{4-[(dodecyl amino) carbonyl] benzyl }-the L-phenylalanine;
[4-[(dodecyl amino) and carbonyl] benzyl } (3-Phenoxyphenyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (the different Phenoxyphenyl of 2-) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-iodophenyl) amino] (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [3-fluoro-4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
((3-chloro-2-aminomethyl phenyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4 '-((carboxyl carbonyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino)-1,1 '-xenyl-2-carboxylic acid;
((2, the 4-dichloro benzyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (1-phenyl propyl) amino] (oxo) acetic acid;
([2-(4-chlorphenyl) propyl group] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-isopropyl phenyl) amino] (oxo) acetic acid;
([4-benzyloxy] phenyl] and 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-methoxy-benzyl) amino] (oxo) acetic acid;
([(IR)-1-(4-chlorphenyl) ethyl] 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
((3, the 4-dichloro benzyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
((1-benzothiophene-3-ylmethyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
([2-(2, the 6-Dichlorobenzene base) ethyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } 2-[3-(trifluoromethyl) phenyl] and ethyl } amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(3-fluorophenyl) ethyl] amino } (oxo) acetic acid;
([(1S)-1-(4-chlorphenyl) ethyl] 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(1S)-and the 1-phenylethyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(1R)-and the 1-phenylethyl] amino } (oxo) acetic acid;
([3-(benzyloxy) phenyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
N-(carboxyl carbonyl)-N-{4-[(dodecyl amino) carbonyl] benzyl }-the D-phenylalanine;
4-[(dodecyl amino) and carbonyl] phenyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] phenyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo 1-[4-(trifluoromethyl) phenyl] and ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo 1-[4-(trifluoromethyl) phenyl] and ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
([(2-butyl-1-benzofuran-3-yl) methyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
(1-{4-[(dodecyl amino) carbonyl] and phenyl } ethyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(1-{4-[(dodecyl amino) carbonyl] and phenyl } ethyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
(4-{[(4-octyl phenyl) amino] and carbonyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (3-benzyl chloride base) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (3-benzyl chloride base) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ { cyclopenta [4-(trifluoromethyl) phenyl] methyl } [4-(tridecanoyl amino) benzyl] amino } (oxo) acetic acid;
Oxo ([4-(trifluoromethyl) benzyl] { [4-(3-undecyl-1,2,4-oxadiazole-5-yl)-1-naphthyl]-methyl } amino) acetic acid;
Oxo ([4-(trifluoromethyl) benzyl] { [4-(3-undecyl-1,2,4-oxadiazole-5-yl)-1-naphthyl]-methyl } amino) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ { cyclopenta [4-(trifluoromethyl) phenyl] methyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ { cyclopenta [4-(trifluoromethyl) phenyl] methyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ (4-dibenzo [b, d] furan-4-base phenyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-dibenzo [b, d] furan-4-base phenyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [4-(octyloxy) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(octyloxy) benzyl] [4-trifluoromethyl] benzyl } amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
[[2-(3-chlorphenyl) ethyl] (4-the last of the ten Heavenly stems-1-alkynyl benzyl) amino] (oxo) acetic acid;
([2-(3-chlorphenyl) ethyl] { 4-[(1Z)-last of the ten Heavenly stems-the 1-thiazolinyl] benzyl } amino } (oxo) acetic acid;
{ [2-(3-chlorphenyl) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3-chlorphenyl) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo (1R)-and 1-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo (1R)-and 1-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo { [4-(trifluoromethyl) phenyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { [4-(trifluoromethyl) phenyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo (1S)-and 1-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo (1S)-and 1-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
[(3-benzyl chloride base) (4-the last of the ten Heavenly stems-1-alkynyl benzyl) amino] (oxo) acetic acid;
[(3-benzyl chloride base) (4-the last of the ten Heavenly stems-1-alkynyl benzyl) amino] (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
[[2-(3-chlorphenyl) ethyl] (4-suffering-1-alkynyl benzyl) amino] (oxo) acetic acid;
[[2-(3-chlorphenyl) ethyl] (4-suffering-1-alkynyl benzyl) amino] (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) phenyl] amino } (oxo) acetic acid;
((4-the last of the ten Heavenly stems-1-alkynyl benzyl) { 1-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid;
((4-the last of the ten Heavenly stems-1-alkynyl benzyl) { 1-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [2-(3-chlorphenyl) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3-chlorphenyl) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ { [4-(dodecyloxy)-1-naphthyl] methyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ { [4-(dodecyloxy)-1-naphthyl] methyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
[(4-bromobenzyl) (4-suffering-1-alkynyl benzyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-hydroxyl-1-phenylethyl) amino] (oxo) acetic acid;
((4-the last of the ten Heavenly stems-1-alkynyl benzyl) { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid;
((4-the last of the ten Heavenly stems-1-alkynyl benzyl) { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo 4-[(9Z)-14-9-alkene acylamino-] benzyl } [4-(trifluoromethyl) benzyl] amino } acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ (4-dodecylbenzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-dodecylbenzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [4-({ [(2-butyl-1-benzofuran-3-yl) methyl] amino } carbonyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(4-{[4-(benzyloxy) benzoyl] amino } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (3, the 5-dichloro benzyl) [4-(tridecanoyl amino) benzyl] amino } (oxo) acetic acid;
{ (3, the 5-dichloro benzyl) [4-(tridecanoyl amino) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
The 4-[(4-octyl phenyl) and acetenyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [4-(5-undecyl-1,2,4-oxadiazole-3-yl) benzyl] amino } acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [4-(5-undecyl-1,2,4-oxadiazole-3-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
4-[2-(4-octyl phenyl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(4-{[4-(oxygen base in heptan) phenyl] acetenyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
The 4-[(4-butyl phenyl)] and acetenyl } benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(4-hexyl phenyl)] and acetenyl } benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(4-hexyl phenyl)] and acetenyl } benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo (4-{[4-(amoxy) phenyl] acetenyl } benzyl) [4-(trifluoromethyl) benzyl] amino } acetic acid;
Oxo (4-{[4-(propyl group phenyl) acetenyl] benzyl } [4-(trifluoromethyl) benzyl] amino) acetic acid;
[[2-(3-chlorphenyl) ethyl] (4-12-1-alkynyl benzyl) amino] (oxo) acetic acid;
[[2-(3-chlorphenyl) ethyl] (4-12-1-alkynyl benzyl) amino] (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ (4-suffering-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(11-hydroxyl 11-1-alkynyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(11-methoxyl group-11-oxo 11-1-alkynyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
11-[4-({ (carboxyl carbonyl) [4-(trifluoromethyl) benzyl] amino } methyl) phenyl] 11-10-acetylenic acid;
(4-{[4-(benzyloxy) phenyl] acetenyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(4-{2-[4-(oxygen base in heptan) phenyl] ethyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[2-(4-butyl phenyl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[2-(4-hexyl phenyl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[2-(4-hexyl phenyl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo (4-{2-[4-(amoxy) phenyl] ethyl } benzyl) [4-(trifluoromethyl) benzyl] amino } acetic acid;
Oxo (4-{2-[4-(propyl group phenyl) ethyl] benzyl } [4-(trifluoromethyl) benzyl] amino) acetic acid;
11-[4-({ (carboxyl carbonyl) [4-(trifluoromethyl) benzyl] amino } methyl) phenyl] hendecanoic acid;
{ [4-(11-hydroxyl undecyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-12-1-alkynyl benzyl) [4-(trifluoromethyl) phenyl] amino } (oxo) acetic acid;
{ (4-12-1-alkynyl benzyl) [4-(trifluoromethyl) phenyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo ([4-(trifluoromethyl) benzyl] { 4-[2-(3-undecyl-1,2,4-oxadiazole-5-yl) ethyl] benzyl } amino) acetic acid;
Oxo ([4-(trifluoromethyl) benzyl] { 4-[2-(3-undecyl-1,2,4-oxadiazole-5-yl) ethyl] benzyl } amino) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
4-[2-(3-octyl group-1,2,4-oxadiazole-5-yl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[2-(3-octyl group-1,2,4-oxadiazole-5-yl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
4-[(4-octyl group benzoyl) and amino] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(4-octyl group benzoyl) and amino] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo { [(1-tridecanoyl piperidin-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
{ { [1-(4-octyl group benzoyl) piperidin-4-yl] methyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ { [1-(4-octyl group benzoyl) piperidin-4-yl] methyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [(3-the last of the ten Heavenly stems-1-alkynyl-1-benzofuran-5-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [(3-12-1-alkynyl-1-benzofuran-5-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo (3-[(4-propyl group phenyl) acetenyl]-1-benzofuran-5-yl } methyl) [4-(trifluoromethyl) benzyl] amino } acetic acid;
[(4-12-1-alkynyl benzyl) (4-luorobenzyl) amino] (oxo) acetic acid;
[two (4-suffering-1-alkynyl benzyl) amino] (oxo) acetic acid;
{ [(6-12-1-alkynyl pyridin-3-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (3-12-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [2-(2-fluorophenyl) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(2-fluorophenyl) ethyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(2-fluorophenyl) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3, the 4-Dichlorobenzene base) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3, the 4-Dichlorobenzene base) ethyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3, the 4-Dichlorobenzene base) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
[2-(1,1 '-xenyl-4-yl) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
[2-(1,1 '-xenyl-4-yl) ethyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
[2-(1,1 '-xenyl-4-yl) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
Oxo { 5,6,7,8-naphthane-1-base [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { 5,6,7,8-naphthane-1-base [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
[[4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] (5,6,7,8-naphthane-1-yl) amino] (oxo) acetic acid;
(1,1 '-xenyl-3-ylmethyl) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
(1,1 '-xenyl-3-ylmethyl) [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
(1,1 '-xenyl-3-ylmethyl) [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (1-benzothiophene-3-ylmethyl) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (1-benzothiophene-3-ylmethyl) [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (1-benzothiophene-3-ylmethyl) [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
Oxo { [2-(trifluoromethyl) benzyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { [2-trifluoromethyl] benzyl } [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
{ [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [3-(trifluoromethyl) benzyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { [3-(trifluoromethyl) benzyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
{ [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (2-methoxy-benzyl) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (2-methoxy-benzyl) [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (2-methoxy-benzyl) [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
Oxo the 4-[(trifluoromethyl) and sulfonyl] benzyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo the 4-[(trifluoromethyl) and sulfonyl] benzyl } [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
([4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] { the 4-[(trifluoromethyl) sulfonyl] benzyl } amino) (oxo) acetic acid;
{ 1,3-benzo dioxole-5-base [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ 1,3-benzo dioxole-5-base [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ 1,3-benzo dioxole-5-base [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [(4-12-1-alkynyl-1-naphthyl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [(4-the last of the ten Heavenly stems-1-alkynyl-1-naphthyl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [(4-the last of the ten Heavenly stems-1-alkynyl-1-naphthyl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [4-(4-undecyl-1,3-thiazoles-2-yl) benzyl] amino } acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [2-(2-fluorophenyl) ethyl] amino } (oxo) acetic acid;
{ (4-12-1-alkynyl benzyl) [2-(2-fluorophenyl) ethyl] amino } (oxo) acetic acid;
{ { [4-(dodecyloxy)-1-naphthyl] methyl } [2-(2-fluorophenyl) ethyl] amino } (oxo) acetic acid;
{ [2-(2-fluorophenyl) ethyl] [4-(octyloxy) benzyl] amino } (oxo) acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-12-1-alkynyl benzyl) [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ { [4-(dodecyloxy)-1-naphthyl] methyl } [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(octyloxy) benzyl] [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [2-(3, the 4-Dichlorobenzene base) ethyl] amino } (oxo) acetic acid;
[[2-(3, the 4-Dichlorobenzene base) ethyl] (4-12-1-alkynyl benzyl) amino] (oxo) acetic acid;
([2-(3, the 4-Dichlorobenzene base) ethyl] { [4-(dodecyloxy)-1-naphthyl] methyl } amino) (oxo) acetic acid;
{ [2-(3, the 4-Dichlorobenzene base) ethyl] [4-(octyloxy) benzyl] amino } (oxo) acetic acid;
(4-[(4-hexyl phenyl) and acetenyl] benzyl } { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid;
{ [4-(5-cyclohexyl penta-1-alkynyl) benzyl] [4-trifluoromethyl] benzyl } amino } (oxo) acetic acid;
3-[(4-hexyl phenyl) and acetenyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(4-ethyl-3-hydroxyl suffering-1-alkynyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (2-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, the L-lysinate;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, tromethane (i.e. (2-amino-2-hydroxymethyl)-1, ammediol) salt;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, the L-arginine salt;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) sodium acetate.
General formula of the present invention (I) chemical compound can be used for preventing and/or treating cardiovascular disease (blocking and heart failure as arteria coronaria).
General formula of the present invention (I) chemical compound prevent and/or treat in the chronic heart failure particularly useful.Particularly, general formula of the present invention (I) chemical compound prevent and/or treat endothelial function disturbance when being selected from heart failure, endothelial NO produces impaired and peripheral blood vessel shrinks on the cardiovascular disease that increases particularly useful.
According to another embodiment, provide general formula of the present invention (I) chemical compound to prevent and/or treat purposes in the medicine of cardiovascular disease in preparation.
According to an embodiment preferred, provide general formula of the present invention (I) chemical compound to prevent and/or treat the particularly purposes in the medicine of chronic heart failure of heart failure in preparation.
According to another embodiment, provide general formula of the present invention (I) chemical compound preparation prevent and/or treat heart failure particularly during chronic heart failure endothelial function disturbance, endothelial NO produce impaired and peripheral blood vessel and shrink purposes in the medicine that increases.
According to another embodiment, provide to prevent and/or treat that cardiovascular disease such as arteria coronaria block, the method for heart failure (comprising chronic heart failure), comprise giving general formula (I) chemical compound to the needs therapist.
Methylene amide derivatives of the present invention can adopt such as described conventional method of WO03/064376 and the calm facile parent material of step and make.
Adjuvant, carrier, diluent or excipient that chemical compound of the present invention uses with routine, can put into pharmaceutical compositions and unit dose thereof, such form can adopt for example solid (as the capsule of tablet or filling), or liquid (as solution, suspension, Emulsion, elixir), or filling the capsule of these liquid, they all are used for oral, or the sterilization Injectable solution, are used for parenteral (comprising subcutaneous administration).Such pharmaceutical composition and unit dosage form thereof can comprise the composition of conventional ratio, have or do not have reactive compound or the composition that adds, such unit dosage form can comprise be equivalent to intend adopting every day dosage range suitable effective amount of actives.
Methylene amide derivatives of the present invention is typically with the form administration of pharmaceutical composition.Such pharmaceutical composition can be prepared by the method that pharmaceutical field is known, and comprises at least a reactive compound.In general, chemical compound of the present invention is with pharmaceutically effective dose administration.The amount of actual administered compound is maked decision according to relevant situation (comprising the order of severity of the subject state of an illness, selected route of administration, actual administered compound, patient's age, body weight and individual reaction, patient's symptom etc.) by the doctor.
Pharmaceutical composition of the present invention can various administrations, comprise oral, rectally, percutaneous dosing, subcutaneous administration, intravenous injection, intramuscular injection and intranasal administration.The form of the desirable self-contained liquid of the compositions that oral administration is used, solution or suspension or bulk powder.Yet, more generally be that compositions provides with unit dosage form, is beneficial to accurately decide dose.Term " unit dosage form " refers to be fit to the unit that each dosage of people and other mammalian subject independently separates, and each unit comprises the scheduled volume that calculates the active substance that produces required therapeutic effect, and suitable drug excipient.The typical unit doses form comprises prefill, scheduled volume ampoule or the syringe of fluid composition, or under the situation of solid composite, comprises pill, tablet, capsule etc.In such compositions, the normally a spot of composition of methylene amide derivatives of the present invention (about 0.1 weight % is preferably about 1 weight % to 40 weight % to about 50 weight %), all the other are various carriers and the processing aid that helps to form required dosage form.
The liquid dosage form that is suitable for oral administration can comprise suitable aqueous or non-aqueous carrier, reaches buffer agent, suspending agent and dispersant, coloring agent, correctives etc.Solid dosage forms can comprise the chemical compound of for example any following composition or similarity: binding agent such as microcrystalline Cellulose, tragakanta or gelatin; Excipient such as starch or lactose; Disintegrating agent such as alginic acid, Primogel or corn starch; Lubricant such as magnesium stearate; Fluidizer such as colloidal silica; Sweeting agent such as sucrose or glucide; Or correctives such as Herba Menthae, methyl salicylate, or orange flavoring agent.
The injectable sterile saline that Injectable composition is typically known based on this area or saline or other injectable carrier of phosphoric acid buffer.As mentioned above, in such compositions, the general formula of replacement (I) methylene amide derivatives is a composition in a small amount, and in the scope of 0.05 weight %-10 weight %, all the other are injectable carrier etc. usually.
The composition of above-mentioned oral administration or Injectable composition only are representational.Other material and process technology etc. are at Remington ' s Pharmaceutical Sciences, and the 17th edition, 1985, Marck PublishingCompany, Easton, the 8th part of Pennsylvania has description, and they are included into this description as a reference.
Chemical compound of the present invention can also slow release formulation or from the Atrigel administration.Representational slow-release material also sees the part of quoting among the Remington ' s Pharmaceutical Sciences.
The pharmaceutical dosage form preparation of methylene amide derivatives of the present invention has description in WO03/064376.
To set forth the present invention by some embodiment below, these embodiment are not considered as limitation of the scope of the invention.
Description of drawings
Fig. 1 shows that the stretching reaction (% diastole) of flow mediated after the mice Mesenteric artery is with the phyenlephrinium preshrinking is to flow in the blood vessel (μ l/min).
The Mesenteric artery stretching reaction of flow mediated with normal mouse (zero) and the normal mouse of accepting the NO synthetic inhibitor (left side, ●) or as inductive chronic heart failure (CHF) mice as described in the embodiment 1 (right side, ●) compare.
Fig. 2 show induced chronic heart failure (CHF) the mice Mesenteric artery with the phyenlephrinium preshrinking after the stretching reaction (% diastole) of flow mediated to flow in the blood vessel (μ l/min).
The Mesenteric artery stretching reaction of untreated CHF mice flow mediated (left and right, zero) is and with 10
-5The Mesenteric artery stretching reaction of CHF mice flow mediated after M The compounds of this invention (1) is handled (left side, ●) and with 10
-6The Mesenteric artery stretching reaction of CHF mice flow mediated after M The compounds of this invention (1) is handled (right side, ●) compare, described as embodiment.
After this following abbreviation is used for appended embodiment:
Min (minute), μ m (micron), μ l (microlitre), M (mole), ACE (angiotensin converting enzyme), CHF (chronic heart failure), FMD (diastole of flow mediated), NO (nitrous oxide), PTPs (Protein Tyrosine Phosphatases).
The embodiment bioassay
In order to represent general formula (I) chemical compound, general formula (I) chemical compound can be done following test in the activity that the stretching reaction of flow mediated after the chronic heart failure recovers.
The NO of flow mediated discharges and can do external assessment on periphery small artery (promptly at heart failure time impel resistance to increase tremulous pulse), and experiment is carried out on the pressurization tremulous pulse of ex vivo perfusion such as little (diameter＜300 μ m) Mesenteric artery or hind leg tremulous pulse.
Embodiment 1: the coronary occlusion model
According to Varin etc. 1999 (Circulation, 99, the 2951-2957) model of Jian Liing induces C57BL6 mice (n=12) to produce chronic heart failure with coronary ligation.This models show is being kept on the background to the reaction of acetylcholine of NO mediation, and chronic heart failure has eliminated that flow is induced, the arteriolar diastole of periphery of NO mediation.
With mouse anesthesia, practice artificial respiration and thoracotomy (pleural space incision).With left main coronary artery in the initiating terminal ligation.Operation causes left ventricle that about 40% infraction takes place.This mouse model, the mortality rate after the left ventricle infraction is 40-50%.
Behind the coronary ligation when 7 days and 2 months, close under the situation in the thoracic cavity and the progress of heart failure to be assessed with ultrasoundcardiogram.Sham-operation (normally) mice except tremulous pulse not by the ligation, accept same processing.
Every group of 6 mices, myocardial infarction survival mice continues on for this research.
After 2 months, mouse anesthesia, row laparotomy (incision abdominal cavity).Under anatomic microscope, cutting out partial Mesenteric artery (diameter 250-350 μ m) is the equal intubate in intestinal segment two ends of 1.5-2.0mm with length carefully, changes arterial pulse recording instrument (Living Systems Instrumentation) over to, is forced into 60mmHg.
Using the phyenlephrinium preshrinking (with 10
-5M was hatched 2 minutes) reach shrink plateau after, the diastole (FMD) of evaluates traffic mediation, promptly blood vessel is replied flow in the tube chamber progressively increases the caliber that (0-200 μ l/min) produced and changes.
1) endothelial function disturbance during the mouse core force failure
On this model of chronic heart failure, the stretching reaction (diastole of flow mediated) that blood flow is increased roughly has been eliminated (diastole during flow 200ml/min: sham-operation: 24 ± 2%, CHF:5 ± 1%).
As shown in Figure 1, normal tremulous pulse is giving NO synthetic inhibitor (NG-nitro-L-arginine, 10
-5M) under the situation, the inhibition of similar stretching reaction is arranged.
2) recovery of the diastole of flow mediated
On the tremulous pulse of having induced chronic heart failure, with { { 4-[(4-hexyl phenyl) acetenyl] benzyl } [4-(trifluoromethyl) benzyl] amino } of the present invention (oxo) acetic acid (1) (with perfusion buffer (Krebs buffer) dilution, from 10
-3M solution dilution to final concentration is 10
-5M and 10
-6M) incubated in vitro is 30 minutes, can make the diastole of flow mediated return to normal level, respectively shown in Fig. 2 left side and the right side.
Present embodiment has shown that The compounds of this invention can recover the endothelial function of chronic heart failure mice significantly.
Claims (19)
1. the optical activity form and the racemic form thereof of methylene amide derivatives shown in the general formula (I) and geometric isomer thereof, its enantiomer, diastereomer, and their pharmaceutically acceptable salt and pharmaceutical active derivant treat and/or prevent purposes in the medicine of cardiovascular disease in preparation
Wherein
R
1Be selected from (C
1-C
15) alkyl, (C
2-C
12) alkenyl, (C
2-C
12) alkynyl, aryl, heteroaryl, (3-8 unit) cycloalkyl or Heterocyclylalkyl, (C
1-C
12) alkylaryl or (C
1-C
12) miscellaneous alkyl aryl, (C
2-C
12) alkenyl-aryl/-heteroaryl, (C
2-C
12) alkynyl-aryl/-heteroaryl;
R
2aAnd R
2bBe selected from H and (C independently of one another
1-C
12) alkyl;
Cy is selected from D and E;
D is selected from the thienyl of replacement and the phenyl of replacement, and wherein substituent group is selected from phenyl, oxadiazole base or is selected from-NH-CO-R
3,-SO
2-NR
3R
3 'With-CO-NR
3R
3 'One or two group,
E is selected from aryl, heteroaryl, (3-8 unit)-cycloalkyl and Heterocyclylalkyl, and wherein aryl, heteroaryl, (3-8 unit)-cycloalkyl and Heterocyclylalkyl are by (C
2-C
18) alkynyl substituted;
R
3And R
3 'Be selected from H, (C independently of one another
1-C
15) alkyl, (C
2-C
12) alkenyl, (C
2-C
12) alkynyl, aryl, heteroaryl, (3-8 unit) cycloalkyl or Heterocyclylalkyl, (C
1-C
12) alkyl-aryl/-heteroaryl, (C
2-C
12) alkenyl-aryl/-heteroaryl, (C
2-C
12) alkynyl-aryl/-heteroaryl.
2. purposes as claimed in claim 1, wherein R
2aAnd R
2bBe H.
3. purposes as claimed in claim 1 or 2, wherein Cy is D.
4. as each described purposes, wherein R in the above-mentioned claim
3 'Be H; R
3Be selected from xenyl ethyl, dodecyl, octyl group, 4-amyl group benzyl, 4-phenoxy group phenethyl, ethylenebis dithiocarbamate benzene-2-base, pentadecyl, tridecyl, hexyloxy phenyl or (2-ethyl) hexyl.
5. purposes as claimed in claim 1, wherein Cy is E.
6. purposes as claimed in claim 5, wherein E is phenyl, pyridine radicals, naphthyl or benzofuranyl, by B-R
4Replace, wherein B is an acetenyl, R
4Be (C
6-C
16) alkyl, (3-8 unit) cycloalkyl, (C
1-C
12) alkyl-(3-8 unit) cycloalkyl, phenyl or (C
1-C
12) alkyl-phenyl.
7. purposes as claimed in claim 6, wherein E is by B-R
4The phenyl that replaces, wherein B is an acetenyl, R
4Be (C
6-C
16) alkyl.
8. as each described purposes, wherein R in the above-mentioned claim
1For-CH
2-A or-CH
2-CH
2-A, A are aryl, heteroaryl, (3-8 unit) Heterocyclylalkyl or (3-8 unit) cycloalkyl.
9. as each described purposes, wherein R among the claim 1-7
1Be A, A is aryl, heteroaryl, (3-8 unit) Heterocyclylalkyl or (3-8 unit) cycloalkyl.
10. purposes as claimed in claim 8 or 9, wherein A is selected from phenyl, pyridine radicals, phendioxin, 3-dioxa cyclopentenyl, xenyl, naphthyl, quinoxalinyl, thiazolyl, thienyl, furyl or piperidyl can randomly be selected from 1 or 2 groups replacements of following group: cyano group, halogen, NO
2, (C
1-C
6) alkoxyl, aryloxy group or heteroaryloxy, (C
1-C
6) thio alkoxy, (C
1-C
12) alkyl, (C
1-C
12) alkyl-X, wherein X is a halogen, (C
2-C
12) alkenyl, (C
2-C
12) alkynyl, aryl, heteroaryl, (3-8 unit) cycloalkyl or Heterocyclylalkyl, (C
1-C
12) alkylaryl or heteroaryl, (C
2-C
12) alkenyl aryl or heteroaryl, (C
2-C
12) alkynyl aryl or heteroaryl ,-COR
3,-COOR
3,-CO-NR
3R
3 ',-NHCOR
3, R wherein
3Be (C
1-C
12) alkyl or (C
2-C
12) alkenyl ,-SOR
3,-SO
2R
3,-SO
2NR
3R
3 ', R wherein
3, R
3 'Be selected from H, straight or branched (C independently of one another
1-C
12) alkyl, (C
2-C
12) alkenyl, (C
2-C
12) alkynyl, aryl, heteroaryl, (3-8 unit) cycloalkyl or Heterocyclylalkyl.
11. as each described purposes, wherein R among claim 1-4 or the 8-10
2aAnd R
2bBe H; R
1For-CH
2-A, wherein A is phenyl or thienyl, can choose wantonly by cyano, halogen, methoxyl group, hydroxyl, phenoxy group ,-NO
2, trifluoromethyl replaces; Cy is quilt-SO
2R
3,-CO-NR
3R
3 'The thienyl, phenyl or the xenyl that replace, wherein R
3Be H, R
3Be (C
7-C
12) alkyl.
12. as each described purposes, wherein R among claim 1-4 or the 8-10
2aAnd R
2bBe H; R
1For-CH
2-A, wherein A is phenyl or thienyl, can choose wantonly by cyano, halogen, methoxyl group, hydroxyl, phenoxy group ,-NO
2, trifluoromethyl replaces; Cy is quilt-SO
2R
3,-CO-NR
3R
3 'The thienyl, phenyl or the xenyl that replace, wherein R
3 'Be H, R
3Be (C
7-C
15) alkyl.
13. as each described purposes among claim 1-4 or the 8-10, wherein said methylene amide derivatives is a chemical compound shown in the general formula (I '),
Wherein
R
1Be selected from phenyl, benzyl, phenethyl, 1-methyl-benzyl, can be by (C
1-C
6) the alkyl or cycloalkyl replacement;
Cy is phenyl and xenyl, can be selected from-NH-CO-R
3,-CO-NH-R
3Or R
3The substituent group that replaces De oxadiazole base replaces, wherein R
3Be (C
7-C
15) alkyl.
14. purposes as claimed in claim 13, wherein R
3Be (C
8-C
15) alkyl.
15. as claim 13 or 14 described purposes, wherein R
3Be dodecyl.
16. as each described purposes in the above-mentioned claim, wherein said methylene amide derivatives is selected from following group:
(benzyl 4-[dodecyl amino] and carbonyl } benzyl } amino) (oxo) acetic acid;
Oxo 4-[(pentadecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } acetic acid;
(benzyl 4-[(pentadecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
(benzyl 4-[(tridecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
[benzyl (4-{[dodecyl (methyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
(4-{[dodecyl (methyl) amino] carbonyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
([1-(tert-butoxycarbonyl)-4-piperidyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
({ [1-(tert-butoxycarbonyl)-4-piperidyl] methyl } { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
Oxo { [4-(tridecanoyl amino) benzyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
[benzyl (4-{[4-(hexyloxy) benzoyl] amino } benzyl) amino] (oxo) acetic acid;
Oxo { [4-trifluoromethyl] benzyl } [4-(10-endecatylene acyl amino) benzyl] amino } acetic acid;
Oxo 4-[(9E)-9-tetradecene acyl amino] benzyl } [4-(trifluoromethyl) benzyl] amino } acetic acid;
{ benzyl [4-(tridecanoyl amino) benzyl] amino } (oxo) acetic acid;
4-[(2-hydroxyl dodecyl) and amino] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (the 1-[(4-methoxyphenyl) sulfonyl]-the 4-piperidyl } methyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-carboxyl-1-phenylethyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-methoxyl group-1-Methylethyl) amino] (oxo) acetic acid;
(the 4-bromine 4-[(dodecyl amino) and carbonyl] benzyl } anilino-) (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } anilino-) (oxo) acetic acid;
([2-(3-chlorphenyl) ethyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(3-methoxyphenyl) ethyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(d, 1)-trans-2-phenycyclopropyl] amino } (oxo) acetic acid;
([(d, 1)-trans-2-benzyloxy] cyclopenta) { 4-[((dodecyl amino) carbonyl) benzyl]-amino } (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl }-4-phenoxybenzamine base) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (1,2,3,4-tetrahydrochysene-1-naphthyl) amino] (oxo) acetic acid;
((1-benzyl-4-piperidyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(4-Phenoxyphenyl) ethyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(2-Phenoxyphenyl) ethyl] amino } (oxo) acetic acid;
((2-[1,1 '-xenyl]-4-base ethyl) and 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
(([1,1 '-xenyl]-3-ylmethyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
(3-(benzyloxy) 4-[(dodecyl amino) and carbonyl] benzyl } benzyl) anilino-) (oxo) acetic acid;
([4-(benzyloxy amino) benzyl] { 4-[((dodecyl amino) carbonyl) benzyl] amino } (oxo) acetic acid;
N-(carboxyl carbonyl)-N-{4-[(dodecyl amino) carbonyl] benzyl }-3-phenyl-β-aniline;
4-[(dodecyl amino) and carbonyl] benzyl } [4-(1,2,3-thiadiazoles-4-yl) benzyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-phenylbenzyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (1-phenylethyl) amino] (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [1-(1-naphthyl) ethyl] amino } (oxo) acetic acid;
(benzyl 3-[(dodecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
3-[(dodecyl amino) and carbonyl] benzyl } [4-(methyl sulphonyl) benzyl] amino } (oxo) acetic acid;
((3-cyano group benzyl) { 3-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
3-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
[(4-benzyl chloride base) (3-{[(4-phenylbenzyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
Oxo { [4-({ [2-(2-thienyl) ethyl] amino } carbonyl) benzyl] [4-((trifluoromethyl) benzyl) amino] acetic acid;
Benzyl [(3 '-{ [(2,2-xenyl ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(3-cyano group benzyl) [(3 '-{ [(2,2-xenyl ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(4-benzyl chloride base) [3 '-{ [(2,2-xenyl ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
[(3 '-{ [(2,2-xenyl ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
((3-cyano group benzyl) { [3 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) [1,1 '-xenyl]-the 4-yl] methyl } amino) (oxo) acetic acid;
Oxo [3 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) [1,1 '-xenyl]-the 4-yl] methyl }-[4-(trifluoromethyl) benzyl] amino } acetic acid;
[(3-cyano group benzyl) (3 '-[(octyl group amino) carbonyl] [1,1 '-xenyl]-4-yl } methyl) amino] (oxo) acetic acid;
[(4-benzyl chloride base) (3 '-[(octyl group amino) carbonyl] [1,1 '-xenyl]-4-yl } methyl) amino] (oxo) acetic acid;
(3 '-[(octyl group amino) carbonyl] [1,1 '-xenyl]-4-yl } methyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(3-cyano group benzyl) [(3 '-{ [(3-phenyl propyl) amino] carbonyl } [1,1 '-xenyl]-the 4-yl] methyl } amino } (oxo) acetic acid;
[(3-cyano group benzyl) (3 '-[(dodecyl amino) carbonyl] [1,1 '-xenyl]-the 4-yl } methyl) amino] (oxo) acetic acid;
[(4-benzyl chloride base) (3 '-[(dodecyl amino) carbonyl] [1,1 '-xenyl]-the 4-yl } methyl) amino] (oxo) acetic acid;
(3 '-[(dodecyl amino) carbonyl] [1,1 '-xenyl]-the 4-yl } methyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Benzyl [(3 '-{ [(4-phenylbenzyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(3-cyano group benzyl) [3 '-{ [(4-phenylbenzyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(4-benzyl chloride base) [3 '-{ [(4-phenylbenzyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
Oxo [(3 '-{ [(4-phenylbenzyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
Oxo [(3 '-{ [(4-phenyl butyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
(3-cyano group benzyl) [(3 '-{ [(2- base ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
(4-benzyl chloride base) [(3 '-{ [(2- base ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] amino } (oxo) acetic acid;
[(3 '-{ [(2- base ethyl) amino] carbonyl } [1,1 '-xenyl]-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
((4-benzyl chloride base) { [3 '-({ [2-(4-methoxyphenyl) ethyl] amino } carbonyl) [1,1 '-xenyl]-the 4-yl] methyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-methoxy-benzyl) amino] (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } (4-methyl sulphonyl) benzyl } amino } (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (4-methoxy-benzyl) amino] (oxo) acetic acid;
3-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } { [6-(trifluoromethyl)-3-pyridine radicals] methyl } amino) (oxo) acetic acid;
4-[((carboxyl carbonyl) 3-[(dodecyl amino) and carbonyl] benzyl } amino) methyl] benzoic acid;
(3-[(dodecyl amino) and carbonyl] benzyl } 4-[hydroxyl (epoxy) amino] benzyl }-amino) (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (2-luorobenzyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (2-pyridylmethyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (3-thienyl methyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (4-hydroxybenzyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (4-phenoxy benzyl) amino] (oxo) acetic acid;
(3-[(dodecyl amino) and carbonyl] benzyl } { [6-(trifluoromethyl)-3-pyridine radicals] methyl }-amino) (oxo) acetic acid;
3-[((carboxyl carbonyl) 3-[(dodecyl amino) and carbonyl] benzyl } amino) methyl] benzoic acid;
5-[((carboxyl carbonyl) 3-[(dodecyl amino) and carbonyl] benzyl } amino) methyl]-2-thio phenyl carboxylic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } 4-[hydroxyl (epoxy) amino] benzyl }-amino) (oxo) acetic acid;
((1,3-benzo dioxole-5-ylmethyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-luorobenzyl) amino] (oxo) acetic acid;
[4-[((dodecyl amino) and carbonyl) benzyl] (4-phenoxy benzyl) amino } (oxo) acetic acid;
4-[((carboxyl carbonyl) 4-[(dodecyl amino) and carbonyl] benzyl } amino) methyl] benzoic acid;
5-[((carboxyl carbonyl) 4-[(dodecyl amino) and carbonyl] benzyl } amino) methyl]-2-thio phenyl carboxylic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (2-thienyl methyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (isopropyl) amino] (oxo) acetic acid;
(3, the 5-dichloro benzyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[(3, the 5-dichloro benzyl) (4-{[(3,3-xenyl propyl group) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
[(4-{[(2-[1,1 '-xenyl]-4-base ethyl) amino] carbonyl } benzyl) (3, the 5-dichloro benzyl)-amino] (oxo) acetic acid;
[(1,3-benzo dioxole-5-ylmethyl) (4-{[(2-[1,1 '-xenyl]-4-base ethyl)] amino] carbonyl benzyl] amino] (oxo) acetic acid;
(2,3-dihydro-1H-indenes-1-base 4-[(dodecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
{ 2,3-dihydro-1H-indenes-1-base [4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-pyridylmethyl) amino] (oxo) acetic acid;
([4-(dimethylamino) benzyl 4-[(dodecyl amino) and carbonyl] benzyl } amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (3-pyridylmethyl) amino] (oxo) acetic acid;
((4-cyano group benzyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (1,3-thiazoles-2-ylmethyl) amino] (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } { [2-(4-morpholinyl)-1,3-thiazoles-5-yl] methyl }-amino) (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (4-pyridylmethyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (3-pyridylmethyl) amino] (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (3-hydroxybenzyl) amino] (oxo) acetic acid;
((4-cyano group benzyl) { 3-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[3-[(dodecyl amino) and carbonyl] benzyl } (1,3 thiazol-2-yl methyl) amino] (oxo) acetic acid;
(3-[(dodecyl amino) and carbonyl] benzyl } { [2-(4-morpholinyl)-1,3-thiazoles-5-yl] methyl } amino) (oxo) acetic acid;
((1,3-benzo dioxole-5-ylmethyl) { 3-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-thienyl methyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-pyridylmethyl) amino]] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (3-thienyl methyl) amino]] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-hydroxybenzyl) amino]] (oxo) acetic acid;
3-[((carboxyl carbonyl) 4-[(dodecyl amino) and carbonyl] benzyl } amino) methyl] benzoic acid;
[cyclopenta (5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) amino] (oxo) acetic acid;
[benzyl (5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) amino] (oxo) acetic acid;
((5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) 3-[[hydroxyl (epoxy) amino] and benzyl] amino } (oxo) acetic acid;
[(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) (4-methoxy-benzyl) amino] (oxo) acetic acid;
[(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) (2-luorobenzyl) amino] (oxo) acetic acid;
(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) [4-(methyl sulphonyl)-benzyl] amino } (oxo) acetic acid;
[(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) (4-phenoxy benzyl) amino] (oxo) acetic acid;
4-{[(carboxyl carbonyl) (5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) amino] methyl } benzoic acid;
((5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) { [6-(trifluoromethyl)-3-pyridine radicals] methyl } amino) (oxo) acetic acid;
(5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
[(3-benzyl chloride base) (and 5-[(dodecyl amino) sulfonyl]-the 2-thienyl } methyl) amino] (oxo) acetic acid;
{ [(5-{[(3,3-xenyl propyl group) amino] sulfonyl }-2-thienyl) methyl] [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (3-benzyl chloride base) [(5-{[(3,3-xenyl propyl group) amino] sulfonyl }-2-thienyl) methyl] amino } (oxo) acetic acid;
Oxo { { [5-({ [2-(4-Phenoxyphenyl) ethyl] amino } sulfonyl)-2-thienyl] methyl } [3-(trifluoromethyl) benzyl] amino } acetic acid;
((3-benzyl chloride base) { [5-({ [2-(4-Phenoxyphenyl) ethyl] amino } sulfonyl)-2-thienyl] methyl } amino) (oxo) acetic acid;
[(5-{[(2-[1,1 '-xenyl]-4-base ethyl) amino] sulfonyl }-the 2-thienyl) methyl] [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
((1-[(cyclohexyl amino) carbonyl]-the 4-piperidyl } methyl) 4-[(dodecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
([(1-{[4-(dimethylamino) anilino-] carbonyl }-the 4-piperidyl) methyl] 4-[(dodecyl amino) and carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(1-caproyl-4-piperidyl) methyl] amino } (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } { [1-(3-iodobenzene formoxyl)-4-piperidyl] methyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(1-{ (2E)-3-[3-(trifluoromethyl) phenyl]-the 2-acryloyl group }-the 4-piperidyl) methyl] amino } (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } { [1-(2-quinoxalinyl carbonyl)-4-piperidyl] methyl } amino) (oxo) acetic acid;
[(the 1-[(4-methoxyphenyl) sulfonyl]-the 4-piperidyl } methyl) (4-{[(4-phenoxy benzyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
[{ [1-(3-iodobenzene formoxyl)-4-piperidyl] methyl } (4-{[(4-phenoxy benzyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
Oxo (4-{[(4-phenoxy benzyl) amino] and carbonyl } benzyl) [(1-{ (2E)-3-[3-(trifluoromethyl) phenyl]-the 2-acryloyl group }-the 4-piperidyl) methyl] amino } acetic acid;
4-[(dodecyl amino) and carbonyl] phenyl } [2-(methoxycarbonyl) benzyl]-amino } (oxo) acetic acid;
[[4-([2-(1,1 '-xenyl-4 base) ethyl] amino } carbonyl)-the 2-bromobenzyl] (4-iodine benzyl) amino] (oxo) acetic acid;
[(2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) (4-iodine benzyl) amino] (oxo) acetic acid;
[2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } (4-iodine benzyl) amino] (oxo) acetic acid;
[(2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) (4-iodine benzyl) amino] (oxo) acetic acid;
((4-iodine benzyl) { [4 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl)-1,1 '-xenyl-4 base] methyl } amino) (oxo) acetic acid;
[2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
[4-([2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-the 2-bromobenzyl] [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
(2-bromo-4-{[(4-phenylbenzyl) amino] and carbonyl } benzyl) [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
[2,6-two bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
[4-([2-(1,1 '-xenyl-4 base) ethyl] amino } carbonyl)-2,6 dibromo-benzyls] [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-phenylbenzyls) amino] and carbonyl } benzyl) [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
([(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] [4 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
(4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [(4 '-fluoro-1,1 '-xenyl-3-yl) methyl] amino } (oxo) acetic acid;
(2-bromo-4-{[(4-amyl group benzyl) amino] and carbonyl } benzyl) [2-(trifluoromethoxy)-benzyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-amyl group benzyls) amino] and carbonyl } benzyl) [2-(trifluoromethoxy)-benzyl] amino } (oxo) acetic acid;
Oxo [4 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl)-1,1 '-xenyl-4-yl] methyl }-[2-(trifluoromethoxy) benzyl] amino } acetic acid;
(4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [2-(trifluoromethoxy)-benzyl] amino } (oxo) acetic acid;
[[2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] (3-methoxyl group-benzyl) amino] (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] (3-phenoxy benzyl) amino] (oxo) acetic acid;
[(2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) (3-phenoxy benzyl) amino] (oxo) acetic acid;
[[2,6-two bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] (3-phenoxy benzyl) amino] (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2,6-dibromo-benzyl] (3-phenoxy benzyl) amino] (oxo) acetic acid;
[(2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) (3-phenoxy benzyl) amino] (oxo) acetic acid;
[2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } (3-phenoxy benzyl)-amino] (oxo) acetic acid;
Oxo ((3-phenoxy benzyl) { [4 '-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl)-1,1 '-xenyl-4-yl] methyl } amino) acetic acid;
Oxo [[(4 '-{ [(4-amyl group benzyl) amino] carbonyl }-1,1 '-xenyl-4-yl) methyl] (3-phenoxy benzyl) amino] acetic acid;
[(4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) (3-phenoxy benzyl) amino] (oxo) acetic acid;
[[2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] (2-iodine benzyl) amino] (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] (2-iodine benzyl) amino] (oxo) acetic acid;
[(2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) (2-iodine benzyl) amino] (oxo) acetic acid;
[2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } (2-iodine benzyl) amino] (oxo) acetic acid;
([2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] { [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
([4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] { [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
((2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
((2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino] (oxo) acetic acid;
(2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
([4-([2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2, the 6-dibromo-benzyl] [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
((2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
(2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino] (oxo) acetic acid;
((4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [2 '-(trifluoromethyl)-1,1 '-xenyl-4-yl] methyl } amino) (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] (1,1 '-xenyl-2-ylmethyl) amino] (oxo) acetic acid;
[(1,1 '-xenyl-2-ylmethyl) (2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
((1,1 '-xenyl-2-ylmethyl) { 2-bromo-4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
{ (1,1 '-xenyl-2-ylmethyl) [2,6-two bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] amino } (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2,6-dibromo-benzyl] (1,1 '-xenyl-2-ylmethyl) amino] (oxo) acetic acid;
[(1,1 '-xenyl-2-ylmethyl) (2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) amino] (oxo) acetic acid;
((1,1 '-xenyl-2-ylmethyl) { 2,6-two bromo-4-[(dodecyl amino) carbonyl] benzyl }-amino) (oxo) acetic acid;
(2-bromo-4-{[(4-amyl group benzyl) amino] and carbonyl } benzyl) [4-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-amyl group benzyls) amino] and carbonyl } benzyl) [4-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
(2-bromo-4-{[(4-amyl group benzyl) amino] and carbonyl } benzyl) [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-amyl group benzyls) amino] and carbonyl } benzyl) [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
(4 '-[(dodecyl amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [3-(trifluoromethoxy) benzyl] amino } (oxo) acetic acid;
[[2-bromo-4-({ [2-(4-Phenoxyphenyl) ethyl] amino } carbonyl) benzyl] (4-phenoxy benzyl) amino] (oxo) acetic acid;
[[4-([2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-the 2-bromobenzyl] (4-phenoxy benzyl) amino] (oxo) acetic acid;
[(2-bromo-4-{[(4-amyl group benzyl) amino] carbonyl } benzyl) (4-phenoxy benzyl) amino] (oxo) acetic acid;
[2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } (4-phenoxy benzyl) amino] (oxo) acetic acid;
[[4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2,6-dibromo-benzyl] (4-phenoxy benzyl) amino] (oxo) acetic acid;
[(2,6-two bromo-4-{[(4-amyl group benzyls) amino] carbonyl } benzyl) (4-phenoxy benzyl) amino] (oxo) acetic acid;
{ [4-({ [2-(1,1 '-xenyl-4-yl) ethyl] amino } carbonyl)-2-bromobenzyl] [4-(trifluoromethyl) benzylamino] (oxo) acetic acid;
(2-bromo-4-{[(4-amyl group benzyl) amino] and carbonyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(2,6-two bromo-4-{[(4-amyl group benzyls) amino] and carbonyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo [(4 '-{ [(4-amyl group benzyl) amino] carbonyl }-1,1 '-xenyl-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
2-bromo-4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
2,6-two bromo-4-[(dodecyl amino) and carbonyl] benzyl } [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo [(4 '-{ [(4-amyl group benzyl) amino] carbonyl }-1,1 '-xenyl-4-yl) methyl] [3-(trifluoromethyl) benzyl] amino } acetic acid;
{ (4-dibenzo [b, d] furan-4-base benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-dibenzo [b, d] furan-4-base benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
(4-[(dodecyl amino) and carbonyl] benzyl } 1-[4-(trifluoromethyl) phenyl] and ethyl } amino) (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } 1-[4-(trifluoromethyl) phenyl] and ethyl } amino) (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
(4 '-[(octyl group amino) carbonyl]-1,1 '-xenyl-4-yl } methyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { (4-14-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } acetic acid;
{ (4-12-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [4-(trifluoromethyl) phenyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-methoxyphenyl) amino] (oxo) acetic acid;
((1,2-xenyl ethyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
N-(carboxyl carbonyl)-N-{4-[(dodecyl amino) carbonyl] benzyl }-the L-phenylalanine;
[4-[(dodecyl amino) and carbonyl] benzyl } (3-Phenoxyphenyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (the different Phenoxyphenyl of 2-) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-iodophenyl) amino] (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [3-fluoro-4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
((3-chloro-2-aminomethyl phenyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4 '-((carboxyl carbonyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino)-1,1 '-xenyl-2-carboxylic acid;
((2, the 4-dichloro benzyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (1-phenyl propyl) amino] (oxo) acetic acid;
([2-(4-chlorphenyl) propyl group] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (4-isopropyl phenyl) amino] (oxo) acetic acid;
([4-benzyloxy] phenyl] and 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-methoxy-benzyl) amino] (oxo) acetic acid;
([(IR)-1-(4-chlorphenyl) ethyl] 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
((3, the 4-dichloro benzyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
((1-benzothiophene-3-ylmethyl) { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
([2-(2, the 6-Dichlorobenzene base) ethyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
(4-[(dodecyl amino) and carbonyl] benzyl } 2-[3-(trifluoromethyl) phenyl] and ethyl } amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [2-(3-fluorophenyl) ethyl] amino } (oxo) acetic acid;
([(1S)-1-(4-chlorphenyl) ethyl] 4-((dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(1S)-and the 1-phenylethyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] benzyl } [(1R)-and the 1-phenylethyl] amino } (oxo) acetic acid;
([3-(benzyloxy) phenyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
N-(carboxyl carbonyl)-N-{4-[(dodecyl amino) carbonyl] benzyl }-the D-phenylalanine;
4-[(dodecyl amino) and carbonyl] phenyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(dodecyl amino) and carbonyl] phenyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo 1-[4-(trifluoromethyl) phenyl] and ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo 1-[4-(trifluoromethyl) phenyl] and ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
([(2-butyl-1-benzofuran-3-yl) methyl] { 4-[(dodecyl amino) carbonyl] benzyl } amino) (oxo) acetic acid;
(1-{4-[(dodecyl amino) carbonyl] and phenyl } ethyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(1-{4-[(dodecyl amino) carbonyl] and phenyl } ethyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
(4-{[(4-octyl phenyl) amino] and carbonyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (3-benzyl chloride base) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (3-benzyl chloride base) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ { cyclopenta [4-(trifluoromethyl) phenyl] methyl } [4-(tridecanoyl amino) benzyl] amino } (oxo) acetic acid;
Oxo ([4-(trifluoromethyl) benzyl] { [4-(3-undecyl-1,2,4-oxadiazole-5-yl)-1-naphthyl]-methyl } amino) acetic acid;
Oxo ([4-(trifluoromethyl) benzyl] { [4-(3-undecyl-1,2,4-oxadiazole-5-yl)-1-naphthyl]-methyl } amino) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ { cyclopenta [4-(trifluoromethyl) phenyl] methyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ { cyclopenta [4-(trifluoromethyl) phenyl] methyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ (4-dibenzo [b, d] furan-4-base phenyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-dibenzo [b, d] furan-4-base phenyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [4-(octyloxy) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(octyloxy) benzyl] [4-trifluoromethyl] benzyl } amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
[[2-(3-chlorphenyl) ethyl] (4-the last of the ten Heavenly stems-1-alkynyl benzyl) amino] (oxo) acetic acid;
([2-(3-chlorphenyl) ethyl] { 4-[(1Z)-last of the ten Heavenly stems-the 1-thiazolinyl] benzyl } amino } (oxo) acetic acid;
{ [2-(3-chlorphenyl) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3-chlorphenyl) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo (1R)-and 1-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo (1R)-and 1-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo { [4-(trifluoromethyl) phenyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { [4-(trifluoromethyl) phenyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo (1S)-and 1-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo (1S)-and 1-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
[(3-benzyl chloride base) (4-the last of the ten Heavenly stems-1-alkynyl benzyl) amino] (oxo) acetic acid;
[(3-benzyl chloride base) (4-the last of the ten Heavenly stems-1-alkynyl benzyl) amino] (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
[[2-(3-chlorphenyl) ethyl] (4-suffering-1-alkynyl benzyl) amino] (oxo) acetic acid;
[[2-(3-chlorphenyl) ethyl] (4-suffering-1-alkynyl benzyl) amino] (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) phenyl] amino } (oxo) acetic acid;
((4-the last of the ten Heavenly stems-1-alkynyl benzyl) { 1-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid;
((4-the last of the ten Heavenly stems-1-alkynyl benzyl) { 1-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [2-(3-chlorphenyl) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3-chlorphenyl) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ { [4-(dodecyloxy)-1-naphthyl] methyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ { [4-(dodecyloxy)-1-naphthyl] methyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
[(4-bromobenzyl) (4-suffering-1-alkynyl benzyl) amino] (oxo) acetic acid;
[4-[(dodecyl amino) and carbonyl] benzyl } (2-hydroxyl-1-phenylethyl) amino] (oxo) acetic acid;
((4-the last of the ten Heavenly stems-1-alkynyl benzyl) { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid;
((4-the last of the ten Heavenly stems-1-alkynyl benzyl) { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo 4-[(9Z)-14-9-alkene acylamino-] benzyl } [4-(trifluoromethyl) benzyl] amino } acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ (4-dodecylbenzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-dodecylbenzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [4-({ [(2-butyl-1-benzofuran-3-yl) methyl] amino } carbonyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(4-{[4-(benzyloxy) benzoyl] amino } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (3, the 5-dichloro benzyl) [4-(tridecanoyl amino) benzyl] amino } (oxo) acetic acid;
{ (3, the 5-dichloro benzyl) [4-(tridecanoyl amino) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
The 4-[(4-octyl phenyl) and acetenyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [4-(5-undecyl-1,2,4-oxadiazole-3-yl) benzyl] amino } acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [4-(5-undecyl-1,2,4-oxadiazole-3-yl) benzyl] amino } acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
4-[2-(4-octyl phenyl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(4-{[4-(oxygen base in heptan) phenyl] acetenyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
The 4-[(4-butyl phenyl)] and acetenyl } benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(4-hexyl phenyl)] and acetenyl } benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(4-hexyl phenyl)] and acetenyl } benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo (4-{[4-(amoxy) phenyl] acetenyl } benzyl) [4-(trifluoromethyl) benzyl] amino } acetic acid;
Oxo (4-{[4-(propyl group phenyl) acetenyl] benzyl } [4-(trifluoromethyl) benzyl] amino) acetic acid;
[[2-(3-chlorphenyl) ethyl] (4-12-1-alkynyl benzyl) amino] (oxo) acetic acid;
[[2-(3-chlorphenyl) ethyl] (4-12-1-alkynyl benzyl) amino] (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ (4-suffering-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(11-hydroxyl 11-1-alkynyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(11-methoxyl group-11-oxo 11-1-alkynyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
11-[4-({ (carboxyl carbonyl) [4-(trifluoromethyl) benzyl] amino } methyl) phenyl] 11-10-acetylenic acid;
(4-{[4-(benzyloxy) phenyl] acetenyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
(4-{2-[4-(oxygen base in heptan) phenyl] ethyl } benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[2-(4-butyl phenyl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[2-(4-hexyl phenyl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[2-(4-hexyl phenyl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo (4-{2-[4-(amoxy) phenyl] ethyl } benzyl) [4-(trifluoromethyl) benzyl] amino } acetic acid;
Oxo (4-{2-[4-(propyl group phenyl) ethyl] benzyl } [4-(trifluoromethyl) benzyl] amino) acetic acid;
11-[4-({ (carboxyl carbonyl) [4-(trifluoromethyl) benzyl] amino } methyl) phenyl] hendecanoic acid;
{ [4-(11-hydroxyl undecyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-12-1-alkynyl benzyl) [4-(trifluoromethyl) phenyl] amino } (oxo) acetic acid;
{ (4-12-1-alkynyl benzyl) [4-(trifluoromethyl) phenyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo ([4-(trifluoromethyl) benzyl] { 4-[2-(3-undecyl-1,2,4-oxadiazole-5-yl) ethyl] benzyl } amino) acetic acid;
Oxo ([4-(trifluoromethyl) benzyl] { 4-[2-(3-undecyl-1,2,4-oxadiazole-5-yl) ethyl] benzyl } amino) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
4-[2-(3-octyl group-1,2,4-oxadiazole-5-yl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[2-(3-octyl group-1,2,4-oxadiazole-5-yl) ethyl] and benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
4-[(4-octyl group benzoyl) and amino] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
4-[(4-octyl group benzoyl) and amino] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
Oxo { [(1-tridecanoyl piperidin-4-yl) methyl] [4-(trifluoromethyl) benzyl] amino } acetic acid;
{ { [1-(4-octyl group benzoyl) piperidin-4-yl] methyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ { [1-(4-octyl group benzoyl) piperidin-4-yl] methyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, N-methyl D-glucamine (being 1-deoxidation-1-(methylamino) glucitol) salt;
{ [(3-the last of the ten Heavenly stems-1-alkynyl-1-benzofuran-5-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [(3-12-1-alkynyl-1-benzofuran-5-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo (3-[(4-propyl group phenyl) acetenyl]-1-benzofuran-5-yl } methyl) [4-(trifluoromethyl) benzyl] amino } acetic acid;
[(4-12-1-alkynyl benzyl) (4-luorobenzyl) amino] (oxo) acetic acid;
[two (4-suffering-1-alkynyl benzyl) amino] (oxo) acetic acid;
{ [(6-12-1-alkynyl pyridin-3-yl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (3-12-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [2-(2-fluorophenyl) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(2-fluorophenyl) ethyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(2-fluorophenyl) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3, the 4-Dichlorobenzene base) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3, the 4-Dichlorobenzene base) ethyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [2-(3, the 4-Dichlorobenzene base) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
[2-(1,1 '-xenyl-4-yl) ethyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
[2-(1,1 '-xenyl-4-yl) ethyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
[2-(1,1 '-xenyl-4-yl) ethyl] [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
Oxo { 5,6,7,8-naphthane-1-base [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { 5,6,7,8-naphthane-1-base [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
[[4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] (5,6,7,8-naphthane-1-yl) amino] (oxo) acetic acid;
(1,1 '-xenyl-3-ylmethyl) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
(1,1 '-xenyl-3-ylmethyl) [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
(1,1 '-xenyl-3-ylmethyl) [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (1-benzothiophene-3-ylmethyl) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (1-benzothiophene-3-ylmethyl) [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (1-benzothiophene-3-ylmethyl) [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
Oxo { [2-(trifluoromethyl) benzyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { [2-trifluoromethyl] benzyl } [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
{ [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [3-(trifluoromethyl) benzyl] [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo { [3-(trifluoromethyl) benzyl] [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
{ [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] [3-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (2-methoxy-benzyl) [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (2-methoxy-benzyl) [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ (2-methoxy-benzyl) [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
Oxo the 4-[(trifluoromethyl) and sulfonyl] benzyl } [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
Oxo the 4-[(trifluoromethyl) and sulfonyl] benzyl } [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } acetic acid;
([4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] { the 4-[(trifluoromethyl) sulfonyl] benzyl } amino) (oxo) acetic acid;
{ 1,3-benzo dioxole-5-base [4-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ 1,3-benzo dioxole-5-base [3-(3-undecyl-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ 1,3-benzo dioxole-5-base [4-(3-octyl group-1,2,4-oxadiazole-5-yl) benzyl] amino } (oxo) acetic acid;
{ [(4-12-1-alkynyl-1-naphthyl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [(4-the last of the ten Heavenly stems-1-alkynyl-1-naphthyl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [(4-the last of the ten Heavenly stems-1-alkynyl-1-naphthyl) methyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
Oxo { [4-(trifluoromethyl) benzyl] [4-(4-undecyl-1,3-thiazoles-2-yl) benzyl] amino } acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [2-(2-fluorophenyl) ethyl] amino } (oxo) acetic acid;
{ (4-12-1-alkynyl benzyl) [2-(2-fluorophenyl) ethyl] amino } (oxo) acetic acid;
{ { [4-(dodecyloxy)-1-naphthyl] methyl } [2-(2-fluorophenyl) ethyl] amino } (oxo) acetic acid;
{ [2-(2-fluorophenyl) ethyl] [4-(octyloxy) benzyl] amino } (oxo) acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-12-1-alkynyl benzyl) [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ { [4-(dodecyloxy)-1-naphthyl] methyl } [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(octyloxy) benzyl] [2-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [2-(3, the 4-Dichlorobenzene base) ethyl] amino } (oxo) acetic acid;
[[2-(3, the 4-Dichlorobenzene base) ethyl] (4-12-1-alkynyl benzyl) amino] (oxo) acetic acid;
([2-(3, the 4-Dichlorobenzene base) ethyl] { [4-(dodecyloxy)-1-naphthyl] methyl } amino) (oxo) acetic acid;
{ [2-(3, the 4-Dichlorobenzene base) ethyl] [4-(octyloxy) benzyl] amino } (oxo) acetic acid;
(4-[(4-hexyl phenyl) and acetenyl] benzyl } { 1-methyl isophthalic acid-[4-(trifluoromethyl) phenyl] ethyl } amino) (oxo) acetic acid;
{ [4-(5-cyclohexyl penta-1-alkynyl) benzyl] [4-trifluoromethyl] benzyl } amino } (oxo) acetic acid;
3-[(4-hexyl phenyl) and acetenyl] benzyl } [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ [4-(4-ethyl-3-hydroxyl suffering-1-alkynyl) benzyl] [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (2-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, the L-lysinate;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, tromethane (i.e. (2-amino-2-hydroxymethyl)-1, ammediol) salt;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) acetic acid, the L-arginine salt;
{ (4-the last of the ten Heavenly stems-1-alkynyl benzyl) [4-(trifluoromethyl) benzyl] amino } (oxo) sodium acetate.
17. as each described purposes in the above-mentioned claim, wherein, cardiovascular disease is a heart failure.
18. as each described purposes in the above-mentioned claim, wherein, cardiovascular disease is chronic heart failure.
19. as each described purposes in the above-mentioned claim, wherein, cardiovascular disease is an endothelial function disturbance.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04100778.2 | 2004-02-27 | ||
| EP04100778 | 2004-02-27 | ||
| PCT/EP2005/050823 WO2005082347A1 (en) | 2004-02-27 | 2005-02-25 | Use of methylene amide derivatives in cardiovascular disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1933827A true CN1933827A (en) | 2007-03-21 |
| CN1933827B CN1933827B (en) | 2011-07-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2005800087220A Expired - Fee Related CN1933827B (en) | 2004-02-27 | 2005-02-25 | Use of methylene amide derivatives in preparing medicine for treating and/ or preventing heart failure |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US20070185118A1 (en) |
| EP (1) | EP1732534B1 (en) |
| JP (1) | JP5001138B2 (en) |
| KR (1) | KR101188940B1 (en) |
| CN (1) | CN1933827B (en) |
| AT (1) | ATE401877T1 (en) |
| AU (1) | AU2005216649B2 (en) |
| BR (1) | BRPI0508080A (en) |
| CA (1) | CA2554919C (en) |
| CY (1) | CY1108252T1 (en) |
| DE (1) | DE602005008412D1 (en) |
| DK (1) | DK1732534T3 (en) |
| EA (1) | EA011811B1 (en) |
| ES (1) | ES2308458T3 (en) |
| HK (1) | HK1098073A1 (en) |
| HR (1) | HRP20080367T3 (en) |
| IL (1) | IL177494A (en) |
| NO (1) | NO20064295L (en) |
| PL (1) | PL1732534T3 (en) |
| PT (1) | PT1732534E (en) |
| RS (1) | RS50596B (en) |
| SI (1) | SI1732534T1 (en) |
| UA (1) | UA84453C2 (en) |
| WO (1) | WO2005082347A1 (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100410236C (en) * | 2002-01-29 | 2008-08-13 | 雪兰诺实验室有限公司 | Substituted methylene amide derivatives as protein tyrosine phosphatase modulators |
| JP5198768B2 (en) | 2003-07-21 | 2013-05-15 | メルク セローノ ソシエテ アノニム | Alkynylarylcarboxamide |
| AU2007307599A1 (en) | 2006-10-12 | 2008-04-17 | Institute Of Medicinal Molecular Design. Inc. | N-phenyloxamic acid derivatives |
| US8633245B2 (en) * | 2008-04-11 | 2014-01-21 | Institute Of Medicinal Molecular Design, Inc. | PAI-1 inhibitor |
| WO2013032971A1 (en) | 2011-08-29 | 2013-03-07 | Ticona Llc | Melt-extruded substrate for use in thermoformed articles |
| US8906258B2 (en) | 2011-08-29 | 2014-12-09 | Ticona Llc | Heat-resistant liquid crystalline polymer composition having a low melting temperature |
| CN103764741B (en) | 2011-08-29 | 2015-09-23 | 提克纳有限责任公司 | The melt polymerization of low melt viscosity liquid crystalline polymers |
| WO2013032981A1 (en) | 2011-08-29 | 2013-03-07 | Ticona Llc | High flow liquid crystalline polymer composition |
| US9074133B2 (en) | 2011-08-29 | 2015-07-07 | Ticona Llc | Thermotropic liquid crystalline polymer with improved low shear viscosity |
| TW201313884A (en) | 2011-08-29 | 2013-04-01 | Ticona Llc | Solid-state polymerization of a liquid crystalline polymer |
| US9045685B2 (en) | 2011-08-29 | 2015-06-02 | Ticona Llc | Cast molded parts formed from a liquid crystalline polymer |
| JP2014525498A (en) | 2011-08-29 | 2014-09-29 | ティコナ・エルエルシー | High fluidity liquid crystal polymer composition |
| CN103764623B (en) | 2011-08-29 | 2016-04-27 | 提克纳有限责任公司 | Aromatic amide compounds |
| WO2014095815A1 (en) | 2012-12-17 | 2014-06-26 | Shell Internationale Research Maatschappij B.V. | Integrated gas-to-liquid condensate process |
| WO2014130275A2 (en) | 2013-02-22 | 2014-08-28 | Ticona Llc | High performance polymer composition with improved flow properties |
| CN113912988A (en) | 2013-06-07 | 2022-01-11 | 提克纳有限责任公司 | High strength thermotropic liquid crystalline polymers |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60028791T2 (en) * | 1999-09-10 | 2007-05-24 | Novo Nordisk A/S | MODULATORS OF THE PROTEIN TYROSINE PHOSPHATASE (PTPASES) |
| US6627767B2 (en) * | 2000-08-29 | 2003-09-30 | Abbott Laboratories | Amino(oxo) acetic acid protein tyrosine phosphatase inhibitors |
| DE10117823A1 (en) * | 2001-04-10 | 2002-10-17 | Merck Patent Gmbh | New N-phenyl-oxalamide derivatives, are factor Xa and factor VIIa inhibitors useful e.g. for treating thrombosis, myocardial infarction, inflammation, angina pectoris or tumor diseases |
| AR034374A1 (en) * | 2001-06-07 | 2004-02-18 | Wyeth Corp | COMBINATION OF A PTPASA INHIBITOR AND AN ACE INHIBITOR |
| US20030022896A1 (en) * | 2001-06-07 | 2003-01-30 | Wyeth | PTPase inhibitors for improving cardiovascular risk profile |
| CN100410236C (en) * | 2002-01-29 | 2008-08-13 | 雪兰诺实验室有限公司 | Substituted methylene amide derivatives as protein tyrosine phosphatase modulators |
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- 2005-02-25 DE DE602005008412T patent/DE602005008412D1/en active Active
- 2005-02-25 SI SI200530349T patent/SI1732534T1/en unknown
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- 2005-02-25 PL PL05716814T patent/PL1732534T3/en unknown
- 2005-02-25 AT AT05716814T patent/ATE401877T1/en active
- 2005-02-25 EP EP05716814A patent/EP1732534B1/en active Active
- 2005-02-25 WO PCT/EP2005/050823 patent/WO2005082347A1/en active Application Filing
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- 2005-02-25 BR BRPI0508080-0A patent/BRPI0508080A/en not_active IP Right Cessation
- 2005-02-25 DK DK05716814T patent/DK1732534T3/en active
- 2005-02-25 ES ES05716814T patent/ES2308458T3/en active Active
- 2005-02-25 PT PT05716814T patent/PT1732534E/en unknown
- 2005-02-25 CN CN2005800087220A patent/CN1933827B/en not_active Expired - Fee Related
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- 2005-02-25 UA UAA200609879A patent/UA84453C2/en unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| ES2308458T3 (en) | 2008-12-01 |
| CN1933827B (en) | 2011-07-27 |
| RS50596B (en) | 2010-05-07 |
| CY1108252T1 (en) | 2014-02-12 |
| IL177494A (en) | 2011-06-30 |
| JP5001138B2 (en) | 2012-08-15 |
| DE602005008412D1 (en) | 2008-09-04 |
| DK1732534T3 (en) | 2008-11-17 |
| PL1732534T3 (en) | 2008-12-31 |
| JP2007524701A (en) | 2007-08-30 |
| KR101188940B1 (en) | 2012-10-08 |
| AU2005216649B2 (en) | 2010-09-09 |
| HK1098073A1 (en) | 2007-07-13 |
| EP1732534B1 (en) | 2008-07-23 |
| CA2554919C (en) | 2013-04-16 |
| UA84453C2 (en) | 2008-10-27 |
| PT1732534E (en) | 2008-08-08 |
| WO2005082347A1 (en) | 2005-09-09 |
| ATE401877T1 (en) | 2008-08-15 |
| HRP20080367T3 (en) | 2008-09-30 |
| KR20060129066A (en) | 2006-12-14 |
| SI1732534T1 (en) | 2008-10-31 |
| EA011811B1 (en) | 2009-06-30 |
| US20070185118A1 (en) | 2007-08-09 |
| EP1732534A1 (en) | 2006-12-20 |
| IL177494A0 (en) | 2006-12-31 |
| BRPI0508080A (en) | 2007-07-17 |
| NO20064295L (en) | 2006-09-22 |
| CA2554919A1 (en) | 2005-09-09 |
| AU2005216649A1 (en) | 2005-09-09 |
| EA200601511A1 (en) | 2007-02-27 |
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